Addiction and the Brain Flashcards
(275 cards)
1
Q
what are neurons?
A
A nerve cell, building blocks of the CNS, they receive, process and transmit info throughout the body
2
Q
what are neurotransmitters?
A
They are chemical messengers that allow neurons to communicate with each other
3
Q
what is dopamine?
A
DA: is a classical neurotransmitter, often referred to as “feel good” due to its involvement in the reward system.
4
Q
what is the association of amphetamines and cocaine to dopamine?
A
They have an impact on dopamine neurotransmission, cocaine blocks dopamine reuptake and amphetamines increase dopamine release
5
Q
what is nonadrenalin?
A
NA: is a classical neurotransmitter involved in the bodys “fight-or-flight” response. plays a role in alertness and arousal/excitment
6
Q
what is the association of amphetamines and cocaine on nonadrenaline?
A
they both affect the levels in the brain, amphetamines can increase the release from neurons, and cocaine can block reuptake leading to a buildup in the synaptic cleft = amplifying fight or flight response and can lead to addiction
7
Q
what is serotonin?
A
5-hydroxytryptamine, 5-HT: is a classical neurotransmitter associated with happiness and love
8
Q
what are the effects of ecstasy on serotonin?
A
effects of levels in the brain: increased serotonin release, leading to depletion of stores in brain leading to depression etc
9
Q
what is acetylcholine?
A
ACh: is a classical neurotransmitter associated with focus, learning and memory
10
Q
what are the effects of nicotine on acetylcholine?
A
nicotine acts as a stimulant by mimicking ACh, binds to nicotinic ACh receptors which stimulates the release of varieous neurotransmitters, over times changes sensitivity of ACh receptors = desensitisation
11
Q
What is a agonist?
A
+ Is a substance that binds to a specific receptor and activates it, mimicking the action of a natural ligand (neurotransmitter)
12
Q
What is an Antagonist?
A
- is a substance that binds to a specific receptor but blocks the action or the natural ligand or other agonists
13
Q
What is an autoreceptor?
A
:is a type of receptor located on the presynaptic neuron thast sensitive to the neurotransmiiter that the neuron itself releases, allowing the neuron to self-regulate releasing or not releasing to prevent flooding
14
Q
What are catecholamines?
A
:Are a group of neurotransmitters and hormones known for their role in the body stress response (regulation of blood pressure, heart rate and metabolic processes), they’re derived from the amino acid tyrosine
15
Q
what are the two main neurotransmitter examples of catecholamines?
A
dopamine and nonadrenaline
16
Q
what is the effect of risperidone on dopamine?
A
is an atypical antipsychotic medication, which blocks DA receptors in the brain, used in schiz and bipolar treatment
17
Q
what are the effects of ritalin on DA AND NA uptake?
A
Ritalin (methylphenidate) is a stimulant medication used to treat ADHD/narcolepsy/sleep disorder. it blocks DA + NA uptake = ends up w/ more dopamine
18
Q
what is RESERPHINE?
A
is a general catecholamine antagonist, inhibits VMAT - a protein responsible for depleting stores of some neurotransmitters to cause sedation, depression etc - used to treat schiz + anxiety etc
19
Q
what are indirect agonists?
A
: a substance that enhances the action of a neurotransmitter but doesnt directly bind to the neurotransmitter receptor itself
20
Q
How is cannabis an example of an indirect agonist?
A
: not chemically/directly related to dopamine system, but THC promotes DA release through cannabinoid receptors, long term use causes DA system dulling
21
Q
what are dopamine pathways?
A
They are neural circuits through which dopamine travels to regulate various physical + psychological functions. These are critical for process like movement, reward, motivation, emotion and hormonal control
22
Q
What is the Mesocortical dopamine pathway?
A
: originates in the ventral tegmental area, but projects to the pfc and regualtes cognition, decision-making, emotion and social behaviour. dysfunction/underactivity is associated w/ negative symptoms of schiz
23
Q
what drugs are used to target the mesocortical dopamine pathway and why?
A
risperidone which promotes DA in the PFC, are used to reduce symptoms of apathy, lack of motivation and cognitive impairments etc
24
Q
What is the mesolimbic dopamine pathway?
A
: originates in the ventral tegmental area and projects to the nucleus accumbens + other limbic areas (amygdala/hippocampus), its involved in reward/ motivation + feeling of pleasure so plays role in reinforcing behaviours and the development of addiction
25
what does overactivity/underactivity in the mesolimbic dopamine pathway cause?
overactivity causes (high dopamine) is linked to addiction, positive symptoms of schiz (mania), underactivitiy (low dopamine) is linked to depression, anhedonia, apathy
26
why are drugs used to target the mesolimbic dopamine pathway?
aim to modulate dopamine activity in the reward and motivation system of the brain, they are used to treat schiz, addiction, depression and parkinsons disease
27
what is the nigrostriatal dopamine pathway?
this is a smaller pathway which starts in the substantia nigra and projects to the striatum and controls movement and motor planning by facilitating the interaction between the basal ganglia and other motor control systems
28
what does degression/ overactivity of the nigrostriatal dopamine pathway cause?
Degression of neurons (low dopamine) in this pathway can cause parkinsons disease - leading to tremors, rigity, - Overactivity (excess dopamine) in the area can cause involuntary movements seen in conditions like tardive dyskinesia
29
why are drugs used to target the nigrostriatal dopamine pathway?
drugs are used for motor control, treats parkinsons, drug induced movement disorders and huntingtons disease
30
what is the tuberoinfundibular dopamine pathway?
: originates in the hypothalamus and projects to the pituitary gland which is associated with hormone release, it regulated the secretion of prolactin from the anterior pituitary gland, playing role in hormonal control
31
what can dysfunction in the tuberoinfundibular dopamine pathway cause?
can result in the hyperprolactimenia, leading to symptoms such as infertility, sexual dysfunction, and galactorrhea (milk production)
32
what is the role of dopamine in the tuberoinfundibular dopamine pathway?
dopamine acts as a prolactin (hormone) antagonist, increased prolactin causes infertility, decreased is rare and there arent signf consequences
33
what are the different dopamine receptors and how are these used to target drugs?
there are D1-5, these are multiple locks fro the same key and are located in different regions, some activate easier (D3- involved inaddiction + impulse control), some not so much (D1- involved in motivation + movement), some excite the neuron (D1-like), while others calm it down (D2-like)
34
how did the results of the British crime surveys change from 1996 to 2000?
in 1996, 30% of adults had tried illegal drugs, this increased to 33% by 2000
35
what were the results of the national survey of drug use and health in 2022 show about Americans?
reports that over 50% of Americans aged 12+ have tried an illicit drug at some point in their lives
36
what are Exposure models of addiction?
:theoretical frameworks - attempt to explain how repeated exposure to addictive substances or behaviors can lead to the development of addiction, all ppl are at risk given sufficient exposure. also that drugs interact + change the brain which create continued motivation to use the drug
37
what is the exposure models explanation of withdrawal?
addicts experience withdrawal when the initial high exhausts the reward/pleasure regions of brain and the drug wears off, it is very aversive. this is negative reinforcement as addict conts taking substance to remove withdrawal symptoms
38
what is the issue with the withdrawal model explanation proposed by conditioned withdrawal?
there are consistent pairings with withdrawal such as an addicts bedroom, which enters into learned associations to become triggers for withdrawal symptoms. if one is exposed enough to these cues, relapse could be triggered
39
what are inhalants?
inhalants are a type of psychomotor stimulant, they're 'volatile; liquids/gases that readily vaporize.
Also they're a diverse range of compounds with wide-ranging effects
40
what are the 3 types of inhalants?
1) volatile solvents: liquid at room temp, give off fumes
2) aerosols: contain solvents/ propellants
3) gases: can be sniffed/inhaled/sprayed into the mouth
41
what are the behavioural effects of acute exposure to inhalants?
euphoria, disinhibition, stimulation then lightheadedness, drowsiness (like alcohol)
42
what are the behavioural effects of heavy exposure to inhalants?
slurred speech ataxia, lethargy, hallucinations, sometimes delusion
43
what are the behavioural effects of very high doses of inhalants?
anaesthesia, coma
44
what was the original use of inhalants?
use dates to early human history related to mystical practices where spiritual leaders inhaled fumes from incense, oils or perfumes to alter consciousness
45
who was Sir Humphry Davy?
british scientist popularized nitrous oxide, cheap substitute for alcohol, who held NO parties and coined th eword "laughing gas" in 1799
46
how are the effects of inhalants mediated in the brain?
theyre rapidly absorbed, so theyre fat soluble. its distributed widely around the brain - especially the striatum, thalamus and deep cerebellar nuclei
47
why are inhalants addictive
dopamine is the substrate of normal reward systems, and is a common factor across a broad spectrum of addictive drugs.
the Mesolimbic pathway also is implicated in natural reward and drugs abuse (the dopamine pathway responsible for rewards, motivation and emotions)
48
what is the evidence that the mesolimbic pathway is activated when consuming inhalants (such as toluene)
Anaesthetized rats - toluene and measured firing in ventral tegmental area (VTA: Riegel and French 1999)
49
what is funada et al (1992) evidence for why inhalants are addictive?
study on mice - placed in 2 connected chambers and toluene distribueted into only one.
exposed rats show + locomotor activity and reduced anxiety behaviour and preference for toluene chamber
= suggesting has stimulating effect on CNS and change in levels of neurotransmitters
50
why are inhalants reinforcing?
the same brain areas are activated in response to toluene as alcohol, opiated and cannabis:
1) .. Inhalants enhance function of GABA and glycine inhibitory receptors
2) Inhalants inhibit excitatory NMDA glutamate receptors (like ketamine)
= similar to alcohol - reduce CNS excitability
51
what are the short term effects of chronic inhalant use?
- Slurred speech
- Runny nose/bleeds
- Tiredness
- Ulcers or irritated nose + mouth
52
what are the long term effects of chronic inhalant use?
- Confusion
- Poor conc
- Depression
- Irritability
- Hostility
- Paranoia
NEUROLOGICAL DAMAGE: cause permanent damage to the NS, leading to conditions such as peripheral neuropathy an encephalopathy
RESPITORY ISSUES: inhaling can irritate respiratory tract and lead to chronic respiratory problems
CARDIOVASCULAR PROBLEMS: can result in irregular heart rhythm and increase the risk of sudden cardiac arrest
53
what is sudden sniffing death syndrome?
SSDS can be caused from use of inhalants, leading to sudden rapid heart rhythms or irregular heart rhythms
54
what is deadly blood disorder (methemoglobinemia)?
can result from inhaling nitrates or poppers which is where the blood becomes physically changed so that is cant deliver oxygen to the body
55
what are the legal issues surrounding inhalant use/being sold?
- Under Scottish law you can be prosecuted for 'recklessly' selling substances to any age group if you suspect they're going to inhale them
Since october 1999, the law makes it an offence to supply gas lighter refills to under 18s, law applies to whole of UK
56
what is gamma hydroxybutyrate? (GHB)
a type of psychomotor stimulant which is a natural product of human metabolism, carb found in our diet (meat,wine etc) and also biologically synthesised from GABA - an amino acid that is structurally similar to GHB.
= a naturally occurring neurotransmitter in the central nervous system and a depressant drug
57
what is Gamma-hydroxybutyrate (GHB) used for?
they're used clinically to treat cateplexy (sudden loss of muscle control experienced by narcoleptics), narcolepsy and alcohol dependency.
often misused for its psychoactive effects
58
what are the behavioural effects of lower doses of GHB? (gamma hydroxybutyrate )
Euphoria
Relaxation and Tranquility
Increased Sociability
Increased Libido
Disinhibition
59
what are the behavioural effects of higher doses of GHB? (gamma hydroxybutyrate )
Drowsiness and Sedation
Dizziness
Loss of Coordination (ataxia)
Nausea and Vomiting
Memory Impairment
Hallucinations
Unconsciousness and Coma
Respiratory Depression
Seizures
Death
60
how quickly and for how long do the effects of GHB (gamma hydroxybutyrate) come on and last for?
The effects typically felt within 15 mins and last for around 3-4 hours
61
what are the 3 forms GHB (gamma hydroxybutyrate ) can come in?
1) a colourless, odourless, bitter or salty-tasting liquid – sold in small bottles or vials
2) a blue coloured liquid
3) crystals or powder (this is less common).
62
what is the interaction between ghb and gaba?
ghb acts as a weak agonist at gaba receptors which are the primary inhibitory receptors in the brain.
= explains depressive effects
63
what is the effect of ghb on dopamine?
Dopamine associated with most drugs and leads to reinforcement. Targets the mesolimbic pathway, induced a sense of reward through dopamine release, thus becomes reinforcing.
64
what is: The GHB Receptor Hypothesis?
one of the main hypotheses regarding the neural mechanisms of GHB:
- ghb effects are mediated by a specific ghb receptor
- high density found on hippocampus and cerebral cortex
65
what is the: The GABA<0xE2><0x82><0x90> Receptor Hypothesis?
one of the main hypotheses regarding the neural mechanisms of GHB:
- ghb mediated pre/post-synaptic gaba release
- GHB acting as a weak agonist at the GABA receptor
66
what are the consequences of long term use of ghb (gamma hydroxybutyrate)?
Can lead to:
- severe memory problems
- heart disease
- Hallucinations
- extreme anxiety
- breathing problems
Some evidence from rats that long term exposure can lead neurological damage, affecting the 'grasping' reflex, as well as alteration in spatial and working memories (pedraza et al 2009)
67
what is zeng et al 2022 research on the adverse effects of ghb usage?
ppts were slower on behavioural tasks that other addicted groups and healthy controls
- Particularly bad at visuospatial, executive function, and memory tasks.
- showed signf decrease in areas of all lobes and central area
68
what are the withdrawal symptoms of ghb?
symptoms reported as insomnia, anxiety and tremors, and at high doses even hallucinations, delirium, extreme agitation and psychosis
69
what % of children in th eus have tried inhalants by 4th grade?
6%
70
what is the issue in australia with inhalants and how have the combatted the issue?
long standing issue with petrol sniffing in indigenous communities
= some areas using non-sniffable fuel called opal
71
what has south africa reduced to keep kids safe from inhalants?
after reports of some being left paralyzed from glue sniffing, glue manufacturer greatly reduced the n-hexane content in their glue products
72
what has been found of the effects of ghb on nacolepsy?
EDS is the most common symptom seen in narcolepsy - causes persistent sleepiness and sudden "sleep attacks" despite getting enough sleep at night
- A systematic review and meta-analysis found ghb was effective in treating EDS and cataplexy, though th medication was also not well tolerated (xu et al 2019)
73
what is the difference between anabolic and androgenic steroids?
Anabolic: increase muscle mass
Androgenic: masculinising/testosterone-like
74
what are steroids (simply) ?
Essentially it is a largely synthetic testosterone - May be used therapeutically to treat condts like low t/hypogonadism in males
- Also used therapeutically e.g. for rheumatoid arthiritis and anaemia and to build muscle for the bed ridden
75
who was brown-séquard in the context of steroids?
- In the 1870’s Brown-Séquard began his experiments with testicular extracts, suggesting some form of chemical/ hormonal understanding
- Testosterone was isolated in the 1930s, and numerous synthetic androgens were quickly developed thereafter
76
in the 1900s, when did steroids begin to be used and for what?
- By the 1940s - benefits of the drugs muscle gain for athletic purposed became realised
- By the 1950s the drug was being used by doctors overseeing body builders and widely used by Russian weightlifters and then began to move into other sporting events
77
in 2016 what happened to all russian weightlifters?
were banned from the olympics with doping being so prevalent
78
what are the ways in which steroids can be taken in athletes?
Steroids taken orally or intramuscularly, also in creams/gels or as patches
79
what does of steroids do endurance athletes/sprinters take compared to body builders?
Endurance athletes and sprinters use low doses, Bodybuilders and strength athletes use up to 100x therapeutic dose
80
what is the problem with oral steroids?
Oral steroids potentially metabolised too fast in liver to act
81
what has been done to overcome the problem of rapid metabolism of steroids?
Additional variants specially designed to avoid problem of rapid metabolism, and to minimize androgenic relative to anabolic effects
82
what are the effects of androgenic steroids?
- psychological effects of 'male' characteristics (aggression etc)
- development + maintanence of libido
- pubertal voice alterations
- increased hair
83
what are the effects of anabolic steroids?
- increased skeletal muscle mass
- improved T-lymphocyte production
- increased size of organs
- retention of electrolytes
- altered distribution of body fat
84
what is the hypotheses that steroids act at androgen receptors?
explains effects of steroids, saying androgen receptors are present in cytoplasm of muscle, androgen binds, activation increases protein synthesis and muscle growth
85
what is the issue with the hypotheses that steroids act at androgen receptors?
Some argue that normally androgen receptors already saturated - so how can steroids work on them?
86
what are the 2 alternative hypotheses that avoid the issue of androgen receptors being already saturated so steroids cant work on them?
Hypothesis 2: steroid treatment induces receptor expression in muscle
Hypothesis 3: androgens are antagonists for glucocorticoid hormones - which are catabolic: decrease protein synthesis, increase in protein breakdown
87
what are common behavioural side effects of chronic steroid use?
The following are reported in steroid users (meeting DSM criteria)
- take more than intended
- can't cut down even though want to
- spend much time obtaining and using
- continue use despite problems use causes
- replace other activities with substance use
88
what are the withdrawal symptoms of chronic steroid use?
fatigue, Depression, insomnia, restlessness, anorexia, decreased libido, dissatisfaction with body image, desire for more steroids
89
what is the explanation for the dependence people gain for steroids?
because steroids arent psychoactive and dont produce euphoria or elicit cravings during withdrawal, perhaps initial reinforcement because of effect on body image
90
what are the possible health consequences of anabolic steroid use?
hypertension, incr blood clotting, incr red blood cells, decreased HDL cholesterol, jaundice, tumors, severe acne
91
what are the behavioural effects of anabolic steroid use?
increased libido, irritability and aggressiveness, dependence
92
what are the behavioural effects specific on men of anabolic steroid use?
testicular shrinkage, reduced sperm counts and possible infertility, prostate enlargement, gynecomastia (breast growth)
93
what are the behavioural effects specific on women of anabolic steroid use?
menstual abnormalities, deepening of the voice, excessive hair growth, especially on face, enlargement of the clit, decreased breast size
94
who is professor david nutt and what were his opinions on steroid use?
chairman of the council's technical committee said It had been estimated that there were tens of thousands of people using steroids to improve the results of training regimens to make themselves look more muscular.
95
what is O'brien et al 1977 study on conditioned withdrawal?
they experimentally induced withdrawal in opiate addicts using an opiate blocker
= ppl w/ blocker + conditioned cue showed + symptoms of withdrawal
96
what is the opponent process model related to addiction?
proposes that drug use triggers two opposing emotional and physiological responses"
- initial positive experience, + reinforcing drug use
subsequent negative experience - body attempts to restore balance (withdrawal)
= creates cycle of addiction
97
what are the key differences between exposure models and susceptibility models of addiction?
EMs: addiction caused by drug + neurological changed (withdrawal + opponent process)
SMs: addiction caused due to individual vulnerabilities - e.g. genetic, psychological/environmental factors
98
what % of ppl have ever used tobacco and what % of users ever became dependent?
75.6% of ppl ever used, 31.9% ever became dependent.
99
why is age a susceptibility factor for addiction?
late teens and early 20s is the peak time for experimenting, when the PFC isnt finished developing
100
what percentage of addiction vulnerability due to heredity based off research?
40-60%
101
how do genes act as a susceptibility factor of addiction?
- Specific genes affect how individuals respond to substances and their likelihood of developing addictive behaviours
- Includes potential impact of dopamine system, e.g. fewer dopamine receptors of increased metabolism
= suggests predisposition, not a guarantee
102
name some susceptibility factors for addiction:
- Drug availability in local are
- Prevalence of drug use in local area
- Neighbourhood - population density, permanence, crime rate
- Parental socioeconomic status
- Criminality in family
- Broken home
- Mental health of parents
- Parent-child attachment
- Peer group norms
- Parent/sibling - attitude to - drug use
- Poor parenting style
- Failure at school
Genetics and role modelling
103
what were the findings of tarter et al 2003 research on susceptibility factors for addiction?
- longitudinal study
- Followed children from age 10 to 19
- Split into high and low-risk groups
- Matched across household income, parent education, parent drug use, etc
Concluded = 'neurobehavioural dishinibition' was greater in the high-risk group and predicted (transition to) illicit drug use
104
what is neurobehavioural disinhibition?
refers to a breakdown in the brain's ability to control impulses, regulate behavior, and suppress inappropriate or maladaptive responses.
105
how does phineas gage (1823-1860) relate to neural disinhibition in drug use?
SEVERE frontal lesion
= unreliable at work, showed callous disregard
Preserved some intellectual function (e.g. memory), but planning ability became very poor
= became an alcoholic and hyper-sexual
This was the birth of the idea that the PFC was used for executive, conscious, decision-making process
106
what is the iowa gambling task?
gages study caused pfc related tasks to develop:
card game where you have to learn which decks are "good" and which are "bad" over time
= most ppl can figure this out but lots of ppl w/ frontal lobe damage cant do this well
= suggest susceptibility for drug use due to pfc damage/underdevelopment
107
what is deroshe-gamonet et al 2004 study on punishment sensitivity?
- Trained rats to give themselves coke, then put them through withdrawal
- Reintroduced coke and provided a cue that previously predicted coke delivery, some relapsed
- Introduced a small experimnetal punishment - shock - for the relapsed rats
Some animals keep wanted the coke even when paired w/ shock
108
how was the flanker task used to study error detection in addicts?
- tasked to identify central letter - recording eeg in coke addicts
= addicts showed reduced frontal activity in response to errors
= suggesting reduced neural sensitivity to improvement in performance
= perhaps addicts have less knowledge of consequences of behaviour
= reduced ability to use this knowledeg to modify behaviour
109
what is perseveration and its role in addiction?
involuntary and often inappropriate repetition of a reward seeking behaviour, despite adverse consequences
= key feature in dependence
110
what are the 3 factors that appear to cause perseveration in adicts?
1) hypersensitivity to rewarding effects of drugs (?followed by hyposensitivity)
2) reduced knowledge of punishing consequences of drug taking
3) reduced ability to use knowledge to modify behaviour
111
what is cannabis produced from?
from the plant cannabis sativa - hemp, found in all plants, concentrated in the sticky resin secreted from the flowering tops of female plants
112
what is the psychoactive agent in cannabis?
Psychoactive agent = ∆9Tetrahydocannabinol (THC)
113
how many non-psychoactive agents are there in cannabis?
70+ other non-psychoactive agents including cannabidiol (CBD)
114
when has the first use of cannabis been recorded?
8000 B.C. - archeological record of hemp cord
115
when did the western world learn of the bioactivity of cannabis use?
1850s
116
what are the 4 forms of cannabis?
MARIJUANA
-dried and clumbled leaves, small stems, flowering
-tops of plant
-usually smoked in joints etc
-THC content varies
- SINSEMILLA
-pollination prevented
-high potency
- HASHISH
-prepared from resin
-potency varies w/ concentration
- HASH OIL
-reduced alcoholic extract
-single drop replaced in a joint
117
What is the thc content in a typical joint?
typically contains 0.5-1 gram
1gram = 4% THC content, 40mg
118
By what % this THC content of samples analysed by ELSohly et al 2016 rise from 1995 to 2015?
from 4% to 15%
119
how does smoking cannabis get THC into the human body?
Burning marijuana results in vaporisation of THC which is absorbed through the lungs into blood plasma
Only about 20% of original THC is absorbed into lungs but can be increased by breath holding (black et al 1998) increased high w/ 15 s breath hold vs 7s
120
what is the half life of smoking cannabis?
half-life of about 20-30 hours
121
where does thc metabolise in the human body when smoked?
= metabolism in liver and fat storage
122
how is thc absorbed into the human body through oral consumption?
ingestion > metabolism in liver > absorbed into blood plasma
= slower/delayed effects relative to smoking - 3-8 hour effects
123
what is the cannabis receptor?
CB1
124
what is the agonist and antagonist of the cannabis receptor CB1?
Agonist = THC
Antagonist = SR141716
125
where in the human brain are cannabis receptors active?
Cannabis receptors active in areas consistent w/ behavioural effects
E.g. hippocampus which is associated w/ spatial memory, globus pallidus, substantia nigra
126
what were the results of huestis et al 2001 study on antagonist effects on effects of cannabis?
- Effects of marijuana reduced by treatment of CB1 antagonist (SR141716)
- 2 groups: placebo control and SR141716 group
Responses recorded over next hour - rating of drug effect and increase in HR
= found SR141716 had lower effects of thc
127
what are the behavioural effects (Iversen 2000) of cannabis?
the buzz = light headedness, dizziness, tingling
the high = euphoria, exhilaration, disinhibition (giggles)
being stoned = calm, floating, slow perception of time, changes in sociability
128
what are the physiological effects of cannabis use?
-increased blood flow to skin
- Increase in HR
- Increase in hunger -demonstration in humans - foltin et al 1988 and rats - williams et al 1998
- Hyperphagia - increased appetite and consumption - williams and kirkman 2002
= induced by THC
= abolished by CB1 antagonist
129
what are the cognitive deficits of cannabis use?
- Oral THC administration impacts verbal memory - curran et al 2002
- Psychomotor functions affected - makes driving dangerous
- Cognitive tolerance in heavy users - hart et al 2001
- Does dependant - low doses have relatively few effects - especially in heavy users
Task dependant - if task demands are high = impaired performance
130
what is conditioned place preference?
behavioural paradigm used in animal research to measure the motivational effects of drugs and other rewarding or aversive stimuli. It assesses the degree to which an animal associates a particular environment with the rewarding or aversive experience.
131
what were the results of valjent and maldonado 2000 study on conditioned place preference to thc?
in mice, only works if mice pre-exposed to thc in home cages (before introduced to experimental apparatus)
= first experience - aversive... then rewarding
132
what is the age of intial peak use of cannabis (brooks et a 1999) ?
17
133
what is the most widely used illicit drug in the UK + US?
cannabis - 4.6%, 14 million in US
134
is cannabis a gateway drug?
Difficult to assess, possible that some users are more disposed to try harder drugs
135
what did compton et al 1990 find about tolerance to thc in humans?
tolerance observed following repeated administration of marijuana or pure THC
136
what did breivogel et al 1990 find about tolerance to thc in animals?
rats - daily injections of THC (10mg/kg) over 3 weeks
Progressive reduction in: CB1 receptor density + activity, some brain areas totally desensitised in 3 weeks
137
what is Precipitated withdrawal?
a sudden and often severe onset of withdrawal symptoms that occurs when an opioid antagonist or partial agonist is administered to an individual who is physically dependent on opioids and still has opioids in their system
138
what were the findings of aceto et al 1996 study on precipitated withdrawal to thc?
Rats given twice daily thc injections
Then given SR141716 - CB1 receptor antagonist
Symptoms of hyperactivity: shaking, face rubbing, scratching
Possibly a consequence of rats being stressed
= increased corticotrophin - releasing hormone (CRH) in precipitated withdrawal rats
139
what therapy can be used to treat cannabis use disorder?
COGNITIVE BEHAVIOURL THERAPY - ppts rewarded w/ vouchers for providing cannabis-free urine samples
- Withdrawal symptoms may be eased by oral consumption of THC - haney et al 2004
140
how effective is CBT on cannabis use disorder?
- Significant relapse - moore and budney 2003
- Useful in short-term, difficult to achieve long-term abstinence
141
what are the behavioural effects of long term cannabis use?
- Chronic cannabis use associated w/ poor education performance:
-more negative attitudes about school
-poorer grades
-increased absenteeism
- Amotivational syndrome:
-apathy: aimlessness: lack of productivity, long term planning and motivation
142
what are some health effects of cannabis use?
- Higher concentrations of carcinogens in cannabis smoke than tobacco
- More tar and carbon monoxide/joint than a cigarette
= Cardiovascular disorders
= Cerebrovascular disorders
etc
143
what are two types of synthetic compounds manufactured from thc and what can they be used for?
DRONABINOL: antimetic for chemotherapy patients
NABILONE: appetite stimulant on AIDS patients
144
what is the average persons daily intake of caffeine?
200-400mg
145
how much caffeine is in one cup of coffee?
80-100mg
146
where is caffeine absorbed once digested and how long does it take?
Caffeine absorbed through the gastrointestinal tract about 20-60 minutes
147
what is the half life of caffeine in plasma?
Plasma half-life of around 4 hours, but usually topped up
148
how is caffeine processed out the body?
Caffeine converted to metabolites by the liver , 95% excreted in urine, 2-5% in faeces, rest through saliva
149
how does caffeine take effect in the brain?
Caffeine acts primarily by clocking adenosine (A1, A2a) receptors in the brain
150
what does Biphasic mean?
means having two distinct phases or stages.
151
what is the biphasic effectof caffeine?
- Low does - stimulant |loco motor activity
- High does - reversed | locomotor activity
152
what are the behavioural effects of low - intermediate doses of caffeine?
variety of positive subjective effects - smith et al 1999:
- Increased alertness
- Reduced tension
- Reduced reaction time
153
what are the behavioural effects of higher doses of caffeine?
Negative effects at higher doses (>400mg; nehlig 2010)
- Tension
- Jitteriness
- Anxiety
- Panic disorder patients may be hypersensitive - panic attacks
154
what are the findings of griffiths et al 1990 on dependence to caffeine?
abstinence = withdrawal symptoms
even in 100mg/day drinkers
= headache, drowsiness.fatigued etc
155
what is the current guideline to how much caffeine a pregnant person can have/day?
200mg/day
156
what is the chemical compound of alcohol?
H H
| |
OH-C-C-OH
| |
H H
ethyl alcohol - ethanol
157
what is the parameter of harms associated with drugs?
physical harm- 1 to 3 (acute, chronic and intravenous harm)
dependence- 4 to 6 (intensity of pleasure, psychological+ physical dependence)
social harms - 7 to 9 (intoxication, other social harms and health-care costs)
158
how is the drug harm scale developed?
- Experts assign score (0-3) for each parameter
- Parameters are averaged to yield overall harm score
159
what are the psychological effects of chronic alcohol consumption?
- Neuropharmacological adaptations, withdrawal symptoms and alcohol dependence
- Severe and chronic cognitive deficits due to brain shrinkage (wernicke-korsako
160
what are the nonspecific effects of alcohol on the brain?
Nonspecific effects:
- interactions with lipid bilayer; mainly at higher concentrations
- disturbs the relationship of protein in membrane
- interacts w/ polar heads of phospholipids
- alters lipid composition
161
what are the specific effects of alcohol on the brain?
- interaction with ligand-gated ion channels (i.e. neurotransmitter receptors) and voltage-gated ion channels; at concentrations within range achieved by common alcohol consumption
- acts as neurotransmitter binding site
- modifies gating mechanism inside channel
- direct interaction w/ channel protein
- stimulates Gs which is linked to adenylyl cyclase
162
how does acute alcohol dampen neural activity ?
e.g. stimulation of inhibitory GABA receptors
163
what is the lethal blood alcohol concentration?
0.45 = coma; lethal for 50& of the population
164
what is the blood alochol conc that causes minimal effects?
0.02-.03 = slight relaxation
165
what is the legal driving limit for alcohol blood conc?
Legal diving limit in UK, except for Scotland, where the limit is 0.05
166
how does alcohol enhance the response of the major inhibitory neurotransmitter GABA?
alcohol acts as indirect agonist at GABA-A receptors i.e. enhances the response of the major inhibitory neurotransmitter GABA
167
what is alcohol induced memory loss?
amnesia: interferes w/ memory especially encoding new info into LT declarative memory
= may range from little memory lapses (cocktail party memory deficits) to black outs
168
what % of 772 undergrads responded 'yes' to aaron white 2002 question?
question: "have you ever awoken after a night of drinking not able to remember things..."
= 51% who'd ever consumed alcohol answered YES
169
what is state dependance as a mechanism of alcohol induced amnesia?
- Information encoded/learnt in a drugged state, may be remembered better if tested in a comparable drugged state, than in a non-drugged state (overton1964)
= alcohol has been shown to render some aspects of declarative memory state dependent
- However, state-dependency appears to account mainly for little memory lapses or fragmentary blackouts - and block blackouts seem to be due to other mechanisms - goodwin 1969
170
what is selective interference with hippocampul memory as a mechanism of alcohol induced amnesia?
- Alcohol mainly interferes with encoding of new declarative information, similar to damage to the hippocampus (such as in patient H.M.) thus, interference with hippocampal synaptic mechanisms of memory may contribute to alcohol-induced amnesia
171
what is Hippocampal long-term potentiation (LTP)?
=is a long-lasting strengthening of synaptic connections between neurons in the hippocampus, a brain region crucial for learning and memory.
It's considered a cellular mechanism that underlies learning and memory formation.
172
how does alcohol distrupt Hippocampal long-term potentiation (LTP)?
a possible mechanism of alcohol induced amnesia: selective interference with hippocampul memory mechanisms:
alc distrupts the induction of hippocampal long-term potentiation (LTP) - an activity-dependent long-lasting increase in synaptic strength and a candidate physiological mechanism of memory - bliss and collingridge 1993
173
what are AMPA receptors?
are a type of ionotropic glutamate receptor found in the central nervous system (CNS), including the brain and spinal cord. They are the primary mediators of fast excitatory synaptic transmission.
174
How is the balance between excitatory and inhibitory neurotransmission altered in response to chronic alcohol?
- Decreased GABA-A receptor function (compensation for acute GABA enhancing effects of acute alcohol)
Increased glutamate receptor stimulation and function (compensating for decreased glutamate release and decreased NMDA receptor function in response to acute alcohol
175
what are the possible effects of an altered balance between excitatory and inhibitory neurotransmission due to chronic alcohol? (decreased GABA-A receptor function + increased glutamate receptor stimulation)
- Many withdrawal symptoms: seizure, tremor, withdrawal anxiety, alcohol craving
Excitotoxic brain damage (resulting in long-term cognitive deficits)
176
what happens to dopamine transmission during alcohol withdrawal?
reduced dopamine transmission:
- reduced nucleus accumbens dopamine during withdrawal
- reduced spontaneous activity of dopaminergic neurons in the VTA
= EFFECT: reduced sensitivity to rewards and reduced motivation
177
what is wernicke-korsakoff syndrome?
- Caused by thiamine deficiency, most commonly in association with alcoholism
- Wernicke syndrome: acute stage, characterised by Ophtalmoplegia (paralysis of eye muscles), confusion, ataxia
- Korsakoff amnesia: remains after treatment of acute Wernicke syndrome if thiamine deficiency lasted too long: global impairment in forming new declarative memory: severe brain 'shrinkage' especially striking degeneration of the mammilary bodies
178
what are opioids?
Narcotic analgesics, i.e. drugs that produce analgesia (reduction of pain) without anaesthesia (loss of all sensation), but promote a sense of relaxation and sleep and at overdoses lead to coma and death.
179
where do opioids come from?
opiates i.e. opium - an extract of the opium poppy plant - and substances directly derived from opium
180
what are some physiological effects of opioids?
- spinal cord and dorsal root ganglian = pain and sensory perception
- lung = decrease respiration, cancer
- adrenal gland = reduce cortisol, affect immune and stress responses
181
what are some key acute effects of opioids?
- analgesia
- cough suppression
- respitory depression
- euphoria
- relaxation and sleep
- constipation
182
what are some key withdrawal symptoms of opioids?
- pain and irritability
- panting and yawning
- Diarrhoea
- dysphoria and depression
183
what is the molecular structure of codeine and its physiological effects?
CH3O
opioid thats less analgesic, but also less side effects and less addictive still very potent cough suppression
184
what is the molecular structure of heroin and its physiological effects?
CH3COO
an opiod that crosses blood-brain barrier more quickly, strong high
= in brain heroin is converted to morphine
185
what drugs are the main cause of overdose deaths?
opioids
186
how can opioid overdose be treated?
Opioid overdose can be treated by injection with the opioid antagonist naloxone.
187
what are the symptoms of an opioid overdose?
- respitory depression
- miosis - pupil constriction
- stupor - unresponsivness
188
what is considered the most harmful drug to others rather than the user? according to nutt et al 2010
alcohol
189
what type of receptors are opioid receptors?
opioid receptors are G-protein-coupled receptors
190
how does activation of opioid receptors effect neurotransmitter release?
Activation of opioid receptors tends to inhibit neural activity or neurotransmitter release of the neuron's carrying the opioid receptor
191
what is nociception?
NOCICEPTION: the neural process of encoding noxious stimuli i.e. stimuli causing tissue damage
192
what is chronic pain?
CHRONIC PAIN: pain that lasts or recurs longer than 3 months
193
what is genetic research and when did it come about?
Considered to be the study of heredity.
i.e., The study of how traits are passed from generation to generation.
Relatively new field of research,
Mid-19th century onwards.
194
who is gregor mendel?
he was credited as the first geneticist (1822-84)
- an Austrian monk and botanist
- spent alot of time breeding and crossbreeding peas
195
what was Gregor Mendels work on crossbreeding peas?
As part of his findings, he noted that peas get one version of each trait from each parent (allele), some seemed to be dominant while others were recessive.
Dominant traits are easily expressed in an organism's phenotype.
On the other hand, recessive traits are only expressed in the absence of an overshadowing dominant trait.
We now know this is due to the pea's genotype - it's genes!
196
what is Heredity?
Heredity:
The passing of physical and mental characteristics from one generation to another.
197
what is a Genotype?
Genotype:
The underlying genetic makeup of a biological organism.
198
what is a Phenotype?
Phenotype:
The observable characteristics of a biological organism. These may be physical or behavioral.
199
what is a Dominant Allele?
Dominant Allele:
An allele that is expressed in the phenotype, even when only one copy is present.
200
what is a Recessive Allele?
Recessive Allele:
An allele that is only expressed when two copies are present in the genotype.
201
what is Mendelian inheritance?
refers to the set of basic principles governing the transmission of hereditary characteristics from parent organisms to their offspring, relies on 2 fundamental laws:
1) Segregation: Traits are either dominant or recessive.
2) Independence: Varieties of each trait sort independently of each other.
202
what is DNA?
Deoxyribonucleic acid (DNA) can be found in the nucleus of every cell of an organism. It is composed of two chains of nucleotides that coil around each other to form a double helix.
203
what are the building blocks of DNA?
- sugar phosphate
- base
- nucleotide
204
what compounds do the 4 bases of a dna strand consist of?
Adenine, Guanine, Cytosine and Thymine. These are always matched A to T & C to G.
205
what are chromatids?
long strands of dna which are tangled together in a cells nucleus when it is active
206
what is condensation in the context of dna?
chromatids (strands of dna) undergo condensation when a cell needs to divide = they coil tight like a spring to form a chromosome
207
how many chromosomes does a typical human have?
46
208
how many genes do humans have
20-25k
209
what is the difference between pleiotropic and polygenic?
Some phenotype traits may be programmed by a single gene (pleiotropic), while others may be influenced by a combination of genes (polygenic).
210
why are recessive traits often more prevalently expressed in males?
X-linked conditions: Some recessive traits are more prevalently expressed in males when compared to females. This is because they may not have a dominant allele on their (much shorter) Y chromosome
211
what is turner syndrome?
Turner Syndrome (effects females; X partially missing).
Effects 1 / 2,500.
212
what is klinefelter syndrome?
Klinefelter Syndrome (effects males; X(+)XY).
Effects 1 / 750
213
what is fragile x syndrome?
genetic disorder that is the most common known single-gene cause of autism spectrum disorder
It is caused by a mutation in the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene located on the X chromosome.
= (repeat on gene for FMR1 protein)
1 / 2:4000 males, 1 / 6000 females.
214
what is triple X syndrome?
xxx - typically assigned female at birth - most have no sever physical differences but may be slightly taller + increased risk of mild developmental and learning challenges
215
what is jacobs syndrome?
XYY - extra Y chromosome, typically assigned male at birth - may be slightly taller + higher chance of learning difficulties but normal sexual development and fertility
216
how are sporadic mutations caused?
Caused by errors or interference in typical cell division. These mutations can happen naturally or be the result of environmental factors (e.g., radiation).
Often includes errors in chromosomal numbers;
217
what is Down’s Syndrome.
sporadic mutation caused by errors or interference in typical cell division:
Effects 1 / 1000.
Majority of cases due to trisomy (extra version) of chromosome 21.
Some symptoms (e.g., facial dysmorphology) evident from birth, while others (e.g., short stature, potential learning difficulties) may only become apparent later in life.
218
what is Williams syndrome?
Effects 1 / 18,000.
Due to microdeletion on chromosome 7 (approx. 25 genes).
Some symptoms (e.g., facial dysmorphology) evident from birth, while others (e.g., potential learning difficulties) may only become apparent later in life.
219
what are genomic studies?
Inspect the genome of specific groups.
Identify allele commonalities.
E.g., Studying an extended family prone to Huntington’s helped identify the genetic markers.
220
what are targeted mutations as a genetic research method?
Mutated lab produced genes are inserted into chromosomes. Usually two types:
These can be defective and fail to produce a specific functional protein (“knockout genes”).
These can also produce new or different proteins (“knock-in genes”).
221
what is a genome?
A genome is the complete set of genetic instructions (DNA) in an organism. It encompasses all of the genes as well as other DNA sequences present in the nucleus of each of its cells.
222
when was to cruelty to animals act?
1876 - first introduction of ethical guidelines for animal use in research
223
when was the first recorded use of animals in research?
starts with romans/greeks - 3000 years ago
224
what is the code of practice the UON follows
UK Research Integrity Office (UKRIO): Code of Practice for Research.
225
when was the first successful transplant?
1954
(50k+ ppl now alive thanks to organ donation + transplant - NHS 2017)
226
what was the The Neubauer Twin Experiments?
beginning in the 1960s and continuing into the 1970s.
= The study involved the secret separation of identical and fraternal twins and triplets adopted by different families. The researchers aimed to study the relative influences of nature (genetics) and nurture (environment) on human development, including personality, intelligence, and mental health.
= strong evidence for the heritability of various traits
= unexpected similarities
227
what were The Los Alamos Plutonium Experiments?
Between 1945 – 1947, 18 people were unknowingly injected with plutonium during unrelated GP visits.
These experiments were crucial for understanding the critical mass of plutonium, its nuclear properties, and the safety procedures necessary for working with this highly radioactive and potentially dangerous material
228
what is the Tuskegee Syphilis Experiment (1932 – ’72).?
Individuals infected with Syphilis.
Lied to about treatment (placebos!).
One of many studies where people have been unknowingly infected.
Fueled congress-lead legislation within the USA.
229
what are hallucinogens?
Induce an altered state of consciousness, characterised by distortions of perception, hallucinations or visions, ecstasy, dissolution of self boundaries and the experience of union with the world
230
what are classical hallucinogens? are the agonists/antagonists and at what receptor?
include plant-derived substance such as:
- psilocybin (form shrooms)
- mescaline (from peyote cactus)
- synthetic drugs such as lsd.
Agonists at serotonin (5-HT) especially 5-HT2A, receptors.
= Altered state of consciousness is primary effect.
231
what are dissociative anasthetics?
Are synthetic drugs such as:
- phencyclidine (pcp)
- ketamine;
= produce anaesthesia (loss of sensation) at higher doses and
= altered states of consciousness at lower doses, including 'disconnection/dissociation' from environment (loss of time sense, feeling of floating/hovering etc) and body (altering perception of body consistency and out of body experience)
= non competitive NMDA receptor antagonists
232
what is teh five-dimensional altered states of consciousness (5DASC) rating scale? what can it be used for (in context of hallucinogens)?
comparison of classical hallucinogens and dissociative anaesthetics:
5 primary dimensions with subdimensions:
- 'oceanic boundlessness' - positively experienced loss of ego boundaries
- 'anxious ego-disintegration' - thought disorder and loss of self control
- 'visionary restructuralization' - referring to perceptual alterations + meaning of perceptions
- 'acoustic alterations' - hypersensitivity to sound and auditory hallucinations
232
233
how long have natural hallucinogens been around for and used?
used for millennia - often as part of rituals
- Plant derived hallucinogens and LSD entered Northern American and European mainstream culture in first half of 20th century
- PCP developed as anaesthetic in mid 1950; ketamine synthesized as safer alternative in 1962 - still used as anaesthetic in humans and in animals
234
what is MDMA?
MDMA (3,4-methylene-dioxymethamphetamine) is an amphetamine w/ strong effects on serotonin transmission
Has stimulant properties, increasing alertness and energy and hallucinogenic-like properties, increasing sociability and talkativeness and inducing an 'altered state of consciousness'
235
what was the proportion of 16-59 year olds using LSD, shrooms and ketamine in crime survey for England + Wales 2017/8?
LSD - 0.4%
shrooms - 0.4%
ketamine - 0.8%
236
what is the harm caused by classical hallucinogenic drugs?
depending on setting and risk in ppl with mental issues
- these drugs cause otherwise virtually no physical harm and no dependance
237
what is the harm caused by ecstasy and dissociative anaesthetics (PCP, ket)?
can cause dependence and cause neurodegeneration, although its debated if typical recreational usage and doses cause neurodegeneration
238
what are the 3 classes of drugs?
class A - considered most harmful:
Cocaine (including crack cocaine)
Ecstasy (MDMA)
Heroin
LSD (acid)
Magic mushrooms
class B - considered less harmful:
Amphetamines (e.g., speed)
Cannabis
Codeine
Ketamine
class C - least harmful:
Anabolic steroids
Benzodiazepines (e.g., Valium)
239
what are indoleamine hallucinogens?
a class of psychedelic drugs that share a common chemical structure based on indoleamine. Indoleamine is a naturally occurring monoamine neurotransmitter that includes compounds like serotonin and melatonin
N-N-H
activate serotonin (5HT2) receptors, and 5HT2A receptor activation is main contributor to their psychological effects
High affinity to serotonin (5HT) receptor
240
what are phenethylamine hallucinogens?
are a class of psychedelic drugs that share a common chemical structure based on phenethylamine, a naturally occurring monoamine compound that acts as a trace amine in the human brain
CH3 - O
activate serotonin (5HT2) receptors, and 5HT2A receptor activation is main contributor to their psychological effects
= High affinity to serotonin (5HT) receptors
241
what are Serotonergic raphe nuclei?
cluster of nuclei found in the brainstem
- primary site of serotonin production in the brain
- in the midbrain innervate large parts of the brain, including many cortical and subcortical forebrain regions
242
what are 5HT2A receptors?
a subtype of serotonin receptors, G protein-coupled receptors
- their activation mainly has stimulatory effects on the neuron (increased transmitter release and increased activity)
-are implicated in the mechanisms of action of certain drugs
- - 5HT2A receptor activation may stimulate excitatory neurons, including in the prefrontal cortex, which may be critical for the hallucinogenic effects (e.g. vollenweider and kometer 2010)
243
how do 5-HT2A receptors mediate subjective effects of psilocybin?
hallucinogen: active compound in shrooms:
has molecular structure similar to serotonin so can bind to 5-HT2A and act as:
244
what is the chemical compound of mdma?
3,4-methylenedioxymethamphetamine
245
what does mdma do in the brain?
- stimulates serotonin release
- also stimulates dopamine release, incl in nucleus accumbens
which is thought to contribute to stimulant and rewarding/reinforcing properties
246
what are dissociative anaesthetics?
a class of psychoactive drugs that produce a unique set of effects, including:
Analgesia: Pain relief.
Anesthesia: Loss of sensation.
Dissociation: A feeling of detachment or disconnection from one's body, surroundings, or reality.
247
how do the effects of dissociative anaesthetics happen?
affecting the activity of the neurotransmitter glutamate in the brain. They act as antagonists at NMDA receptors, which are crucial for:
- Pain perception
- Consciousness
- Memory
also stimulate prefrontal cortex and nucleus accumbens dopamine release
248
what is prefrontal cortical activation as a neural mechanism for hallucinogenic drug effects?
PFC is rich in 5-HT2A receptors. Given the PFC's role in higher-level cognitive functions, it's involved in the complex subjective experiences produced by drugs
249
why might some dissociative anaesthetics have a lower potential for dependence than others?
= this may be partly mediated by the increased meso-corticolimbic dopamine release caused by these drugs
(ketamine, PCP) and mdma
250
when was the first clinical study that reported ketamine anti-depressant effect?
2000
251
what are amphetamines?
a synthetic psychostimulant that in terms of its chemical structure is similar in nature to the neurotransmitter dopamine
252
what is the history of use of ephedra?
type of amphetamine:
- in the 1920s - used for asthma which led to search for synthetic substitute: amphetamine inhaler
- ephedra now banned appetite suppressant
253
what are the mild to moderate behavioural effects of cocaine and other psychostimulants?
- mood amplification: euphoria/dysphoria
- heightened energy
-sleep disturbance
- motor excitement
- talkativeness
- hyperactive ideation
254
what are the severe behavioural effects of cocaine and other psychostimulants?
- irritability, hostility, anxiety, fear, withdrawal
- extreme energy or exhaustion
- insomnia
- anorexia
255
what are the neurotransmitters involved in amphetamine use?
- DA - dopamine
- NA - nonadrenaline
- 5-HT - serotonin
- Unlike cocaine which just blocks catecholamine reuptake (dopamine), amphetamines also actively release these neurotransmitters from nerve terminals
- they also prevent reuptake of nonadrenaline
256
what is DAT?
refers to the dopamine transporter, a protein that regulates dopamine levels in the brain by transporting dopamine back into the presynaptic neuron after it is released
257
what do amphetamine cause in synaptic transmission?
- AMPH taken up by DAT (dopamine transporter) , inside terminal provokes DA release, plus DAT functions in revers to further release DA
- Dopamine reuptake transporters are blocked by cocaine, this results in increased dopamine in the synaptic cleft, leading to behavioural symptoms of cocaine use
258
what does a psychostimulant microinjection to the nucleus accumbens do?
increased locomotor behaviour
259
what does a psychostimulant microinjection to the striatum do?
increased stereotyped behaviours
260
what is a 6-OHDA lesion?
A 6-OHDA lesion refers to a surgical procedure used to create a model of Parkinson's disease in animals
261
what does a 6-OHDA lesion in the striatum cause?
decreased locomotor response following systemic administration of a low-dose psychostimulant
262
what does a amphetamine microinjection in the nucleus accumbens cause?
reinforcing to the animal
263
what does a cocaine microinjection in the nucleus accumbens cause?
not reinforcing to the animal
264
what is amphetamine psychosis?
caused by chronic usage
265
what is griffith et al 1972 study on amphetamine psychosis?
- Ppts (n=7) users but no prior history of psychosis
- Given 10 mg dextroamphetamine every hour for up to 5 days
- All became psychotic within 2-5 days
Delusions mostly auditory, also induced poisoning by experimenters and electric dynamo thought control
266
what are the behavioural effects of chronic use of amphetamines?
- addiction and dependence
- cognitive impairment
- mood disorders
- psychosis
- aggressive behaviour
- sleep disturbances
- physical health decline
266
what are the neurological effects of chronic usage of amphetamines?
1) Neurotransmitter Imbalance: regulation of dopamine, norepinephrine, and serotonin = withdrawal symptoms.
2) Cognitive Impairment: impair memory, attention, and decision-making abilities, affecting daily life and mental health.
3) Amphetamine-Induced Psychosis: result in paranoia, hallucinations, and delusions, resembling symptoms of schizophrenia.
4) Neurotoxicity: can cause nerve cell damage, increasing the risk of seizures and strokes.
Structural Brain Changes: affects neural plasticity, leading to changes in brain structure and function, impacting overall brain
267
what is inada et al 1992 study on tolerance to amphetamines?
- 11 days continuous iv infusion (to total 60mg/kg/day
- 20 mg/kg cocaine challenge
= Schedule produced tolerance
268
what does sensitization to amphetamines cause?
Sensitization leads to increased activity in reward-related brain regions, such as the ventromedial caudate, during reward anticipation.
= This was measured using blood oxygen level dependent (BOLD) signal during functional MRI scans.
269
what are the clinical applications of amphetamines to ADHD?
- Amphetamines such as ritilin - commonly used to treat symptoms to increase focus and decrease inattention, hyperactivity and impulsivity
- Low doses can reduce locomotor activity (hyperactivity) in humans and in rats (cortese et al 2018 kuczenski and segal 2002)
270
what are the clinical applications of amphetamines to narcolepsy?
- Individuals often struggle w/ daytime sleepiness
- Amphetamines stimulate wakefulness during day allowing to function more adequately (morgenthaler et al 2007)
271
what are the clinical applications of amphetamines to BED?
its believed that amphetamines help by increased dopamine and norepinephrine in the synaptic cleft
- In the preclinical studies of binge eating in rats, lisdexamfetamine was shown to reduce chocolate bing eating and revers bing-eating impulsiveness (vickers et al 2015,17)
272
what is lisdexamfetamine?
a amphetamine which can be used to treat ADHD and BED
273
