Drugs Flashcards
(57 cards)
1
Q
what study found that stimulation in the septum is rewarding?
A
- Olds and Milner (1954): study how stimulation of reticular formation could affect learning
- in a test to see if stimulation was aversive, one rat appeared to find it pleasurable
- electrode was mistakenly in the septum instead of the reticular formation
- other rats with septal electrode implants found stimulation of that area rewarding
Stimulation in septum → rewarding
2
Q
what is intracranial self-stimulation? how does this look in rats?
A
- form of instrumental learning that is acquired quickly
- rats respond at very high rates (higher than for food), they learn that pressing the lever → reward
- rats will self stimulate until exhaustion, ignoring food/water to near death, will risk harm to obtain self-stimulation
- multiple brain sites found to support self- stimulation, but some sites don’t self stim, and stim some areas is aversive
- all brain regions that support self stimulation are directly/indirectly connected to the mesolimbic dopamine system
3
Q
what is the mesolimbic dopamine system?
A
- dopamine neurons are projection neurons; all the cell bodies are in midbrain and send axons to many brain regions
- substantia nigra sends dopamine axons to striatum, involved in motor functions
- ventral tegmental area (VTA) is the heart of the mesolimbic DA system, send DA axons via medial forebrain bundle to limbic regions
- projects to PFC, amygdala, and nucleus accumbens (NAc) region of the ventral striatum
4
Q
how is the mesolimbic DA system connected to self-stimulation and reward?
A
- self stimulation increases DA release in the limbic system, particularly the accumbens
- reducing DA transmission reduces self-stimulation (antipsychotic drugs)
- animals will work to have DA agonists infused directly into accumbens
- natural rewards or conditioned stimuli associated with rewards increase DA accumbens release (in absence of self stim later)
- suggests DA plays an important role in reward-related approach behaviours
- all drugs of abuse with high-addiction potential increase DA release in the nucleus accumbens (through different mechanisms)
5
Q
what are the principles of drug action?
A
- tolerance: decreased sensitivity to effects of a drug after repeated use
- withdrawal: rebound reaction to elimination of drug from system after repeated exposure, typically the opposite of the drugs action
- sensitization: some effects of some drugs show increased sensitivity after repeated exposure
6
Q
what are the two types of tolerance?
A
- Metabolic - body (liver) becomes more efficient at metabolizing the drug, less of the drug gets to sites of action
- Functional (pharmacodynamic) - occurs at site in brain/body where drug exerts its effects (ex. # of receptors decreases)
7
Q
does tolerance occur at the same rate for all effects the drug?
A
- tolerance develops to some effect of drugs, not others, and can develop at different rates for different effects
○ ex. heroin causes euphoria and can suppress respiration, tolerance to pleasurable effects develops faster than to respiratory effects
○ heavy users increase dose to obtain a better high, but this can lead to over-use by over-inhibiting respiratory centers
8
Q
why do we go through withdrawal and what determines the severity of withdrawal?
A
- may be viewed as the body’s attempt to maintain homeostasis, additional drug taking can alleviate withdrawal
- drugs cause body/brain to initiate compensatory changes to counteract the effects of the drug → tolerance
- when drugs have been eliminated from system, these changes can linger for some time after → withdrawal
- individuals suffering from withdrawal symptoms are said to physically dependent
Severity of symptoms depends, but usually longer/greater exposure = greater withdrawal symptoms
9
Q
what is conditioned tolerance? what study displayed how tolerance can be conditioned?
A
- conditioned tolerance: tolerance is maximal when drug is administered in environments similar to those where drug effects were experienced previously
- study: give rats 20 shots of alcohol in one environment over 20 days, on test day one group gets alcohol in the same context, other group gets it in different context
- rats receiving test day in same context displayed tolerance, those in different context did not (alcohol causes hypothermia in rats)
- rats that were in the same context were expecting alcohol and subsequent hypothermia, so their body starts to warm (compensatory effect)
10
Q
what is conditioned withdrawal? what study displayed how withdrawal can be conditioned?
A
- conditioned withdrawal: withdrawal elicited by the drug environment or drug associated cues
- study: looked at morphine withdrawal in three groups of rats
- Never received morphine
- Received repeated injections of morphine in one context, withdrawal test assessed in different context
- Received repeated injections of morphine in one context, withdrawal test assessed in same context
- withdrawal was maximal when animals were in the same context where drug effects were previously experienced
- suggests that exposure to drug-related cues can induce conditioned compensatory responses
11
Q
why can tolerance and withdrawal be conditioned?
A
- the brain gets conditioned to cues associated with drug taking → cues trigger compensatory changes in body to prepare for more drug taking
- go to drug context and then don’t take drugs → conditioned withdrawal
○ because there is no drug to counteract the compensatory changes which are usually opposite to those of the drug - take drug in same context → conditioned tolerance
○ because body has prepared itself to counteract the drug
12
Q
what is amphetamine (AMPH) induced locomotion? how do we see this effect sensitized?
A
two test groups
1. get low dose AMPH on day 1 (test dose), then gets daily saline injections for 5 days
2. gets test dose AMPH on day 1, then gets AMPH repeatedly for 5 days
* on test day, both groups get same test dose of AMPH and locomotor response is much greater in the group with repeated exposure (the response has been sensitized)
* locomotor effects of amphetamine are caused by increase in DA release
13
Q
how does sensitization affect dopamine release? what does this tell us about drugs of addiction?
A
- all drugs of abuse that have addictive potential can produce sensitization to their effects on dopamine transmission
- ability for the drugs to trigger dopamine release increases over time
- this leads to more reward-related approach behaviour that could explain addiction
14
Q
what are the three main factors considered when classifying someone has having a substance use disorder?
A
- habitual drug use that persists in spite of the adverse effects on one’s health and social life (may be viewed as a chronically relapsing disorder)
- drug seeking behaviour: disproportionate amount of time spent thinking about and acquiring the drug
- physical dependence: do they suffer from withdrawal from the drug
15
Q
are withdrawal symptoms the cause of addiction?
A
- can contribute to relapse in short term, but may not be a major factor contributing to long lasting effects of addiction
- physical withdrawal last for a few days, but addiction can last a lifetime
16
Q
how do we classify the addictive potential of a drug?
A
1) common sense (do these drugs appear to be habit forming)
2) whether animals will self administer the drug
3) physical dependence
17
Q
what is marijuana? is it addictive and does it involve withdrawal symptoms?
A
- technically defined as a hallucinogen
- active ingredient is THC from cannabis plant
- low addictive potential
- withdrawal symptoms are uncommon, but can occur (they are minor if they do occur)
18
Q
how does marijuana behave in the brain?
A
- cannabinoid receptors found all over the brain (DA system, hippocampus, PFC, amygdala, accumbens)
- neurotransmitter anandamide acts as a retrograde messenger, produced by the postsynaptic side of the neuron unlike normal neurotransmitters
- when anadamide binds, it inhibits presynaptic transmitter release
19
Q
what are the effects of marijuana at lower and higher doses?
A
- lower, social doses: increase sense of well-being, dreamy state, altered sensory perceptions, increased “munchies”
- higher doses: sensory disturbances, emotional intensification, impaired motor, cognitive speech processes
- in some cases, higher doses can produce transient psychotic symptoms (depersonalization, agitation, and paranoia)
20
Q
how does marijuana affect cognitive functions and psychomotor performance?
A
- impaired performance for a variety of verbal, spatial, time estimation, and reaction-time tasks
- given list of words to remember and tested later, poor memory recall after THC consumption
- cannabinoids appear to interfere with all aspects of memory processing
21
Q
what are the health effects of chronic use of marijuana?
A
- there have been no reports of overdose from marijuana
- smoking may damage lungs and reduce testosterone in men
- animal studies suggest it may impair immune resistance
22
Q
what do imaging studies of chronic marijuana smokers show?
A
- associated with reduced activation in PFC/amygdala regions in response to emotional faces
- deficits in appropriately judging emotional and affective cues
23
Q
is there a link between marijuana use and schizophrenia?
A
marijuana may precipitate development of psychosis in young individuals at risk of developing schizophrenia
24
Q
does marijuana have any medicinal effects?
A
- anti-nausea
- analgesia (painkiller)
- appetite stimulant
- potential antidepressant properties
- drug companies are developing compounds that stimulate cannabinoid receptors for treatment of a number of disorders (cancer)
25
how addictive and how prevalent is alcohol use?
* has high addictive potential
* 2/3 of the population consumes alcohol, and 10% of those people eventually develop Alcohol Use Disorder
26
how do the effects of alcohol differ at lower and higher doses?
alcohol has biphasic action
* lower doses: disinhibition, euphoria, relaxation
* higher doses: slurred speech, disrupted motor co-ordination, sedation, coma, death
27
how does alcohol behave in the brain?
* depresses neural firing in multiple ways
* acts as a positive modulator for GABA receptors (like benzodiazepine), don't just turn on GABA receptors
* when GABA binds to the receptor, alcohol increases the receptor’s response
* reduces functioning of NMDA glutamate receptors, which affects our memory
* blocks Ca2+ and other ion channels in neurons, disrupts second messenger systems
28
if alcohol depresses firing, why do lower doses feel like a stimulant?
* alcohol increases activity at GABA receptors and reduces glutamate-NMDA mediated activity
* at low doses, alcohol preferentially inhibits fast-firing GABAergic interneurons
* these interneurons normally suppress activity in the prefrontal cortex (PFC)
* inhibiting the inhibitors = disinhibition of the cortex → increased PFC activity
* higher doses cause broader cortical inhibition because it suppresses many neurons, not just inhibitory ones
○ alcohol increases DA release, but mechanisms not completely understood (mediated partially via interactions with opioid system)
29
how addictive is nicotine and how does it behave in the brain?
* high addictive potential, comes from tobacco
* stimulates nicotinic acetylcholine receptors which increase neural activity
* nicotinic receptors are on DA neurons, main pathway that underlies the addictive properties of the drug
30
what is the effect of nicotine in non-smokers vs. smokers?
* effects in non-smokers: nausea, vomiting, coughing, sweating, abdominal cramps, dizziness, flushing, diarrhea
* effects in smokers: less hungry, more alert, more relaxed
○ over time, many of the aversive effects of nicotine develop tolerance, whereas some of the “rewarding” effects may sensitize
31
what does nicotine withdrawal look like?
* irritability, anxiety, restlessness
* constipation
* difficulty sleeping and concentrating
* increased appetite
32
how are the addictive properties of nicotine linked to the route of administration?
* inhalation of tobacco smoke causes rapid/pulsatile increase in nicotine in blood/brain
* nicotine therapies cause gradual, sustain increases in blood/brain levels of the drug, they are not as reinforcing
33
how common is nicotine addiction in people who experiment with smoking?
* about 70% of people who experiment with smoking become addicted
* compared to 10% for alcohol and 30% for heroin
* 20% of all attempts to quit are successful for less than 2 years
34
what are the positive effects of nicotine use?
* improved attention/cognition
* improves cognition in individuals with alzheimer's or schizophrenia
* decreases risk of parkinson's
35
how addictive are opiates and what are their effects?
* high addictive potential
* in order of potency: fentanyl > heroin > morphine>methadone > codeine
* when taken intravenously, initial wave of intense abdominal orgasmic pleasure that evolves to serene drowsy euphoria
* first rush entices the user to do more, but tolerance builds up and higher doses are needed to get a similar effect (never as good as 1st rush)
36
how do opiates behave in the brain?
* opioid drugs act as agonists for “endogenous opioid” receptors
* enkephalin and endorphin are 2 common endogenous opioid peptides- generally inhibit neural activity
* endogenous opioids mediate analgesia, emotional regulation, sensory/motor integration
* receptors in the accumbens mediate pleasurable aspects of natural rewards (sweet/fatty tastes)
* opioid receptors are on GABA neurons in the VTA. activating these receptors inhibit GABA neurons, disinhibits dopamine neurons
37
what does opioid withdrawal look like?
* withdrawal starts 6-12 hours after last dose
* increase in restlessness, watery eyes/nose, sweating
* followed by a fitful sleep for several hours
* opioids depress CNS function so opioid withdrawal is rebound hyperactivity
* symptoms are typically worse on the 2nd-3rd day and disappear by the 7th day
38
what are the long-term health consequences of opioid use?
* main risks of the intravenous drug user is OD
* either due to using street drugs of unknown potency or conditioned tolerance effects adn use of second-hand needles
* opioid drugs themselves don't have as many health consequences as other drugs
* minor health consequences of long-term use: constipation, pupil constriction, menstrual irregularity, reduced libido
* recent work suggest that long-term cognitive deficits are associated with chronic heroin abuse
39
what are psychostimulants and how addictive are they?
* high addictive potential
* cocaine, amphetamines
40
what are the psychological effects of psychostimulant use?
* increased self-confidence
* alertness, energy
* makes people friendly and talkative
* can alleviate some effects of short-term depression
41
what are the physiological effects of psychostimulant use?
* motor activation (fidgety)
* decreases in appetite
* decreased in need for sleep, increased arousal
* increase in cardiovascular tone
42
what is a drug spree?
* binges where high levels of intake are maintained for 1-3 days
* spree only ends when money runs out or toxicity develops
43
what does psychostimulant withdrawal look like?
* fatigue
* increased appetite
* depression, anhedonia, anxiety
* irritability, agitation or sometimes extreme suspicion
* also an increase in drug craving
* many times, physical withdrawal symptoms are not as visibly apparent at they are for other drugs
* withdrawal symptoms tend to be more prominent with amphetamines (particularly methamphetamine) vs cocaine
44
how do psychostimulants like cocaine and amphetamines behave in the brain?
* in normal DA transmission, DA is released by presynaptic terminal, but is quickly taken back by the DA transporter
* cocaine blocks the DA transporter so that DA that has been released stays out longer
* amphetamines reverse the DA transporter so more DA is released and stays out a lot longer, transporter spits out more DA from the neuron
* both amphetamines and cocaine work on multiple monoamine systems (NE, 5-HT) but the reinforcing effects of the drugs are mediated by actions on DA
45
what are the adverse consequences of long-term psychostimulant use?
* psychosis, seizures, brain damage to monoamine systems, strokes, heart attacks
* brain damage may be the result of strokes (vasoconstriction via increase in noradrenaline release) or DA-induced toxicity
* many stimulant abusers display deficits in cognitive functions mediated by the PFC, which can persist for years after drug abstinence
46
what therapeutic effects do psychostimulants have?
* powerful stimulant that promotes wakefulness
* given to WWII military to reduce need for sleep
* still prescribed for some types of sleep disorders like narcolepsy
* but it reduces REM sleep
* cognitive enhancer that can improve attention, working memory, memory encoding
* enhances cognitive function in healthy humans and in some psychiatric disorders (ADHD, schizophrenia)
* effects on cognition may be mediated by enhancing DA and noradrenaline activity in the PFC
* but, enhancement of these functions comes at the sacrifice of other functions (creative thought)
47
what is the physical dependence model (theory of drug addiction) and what are some problems with it?
drug taking is driven by desire to reduce withdrawal symptoms
* problems: people with addiction often relapse when withdrawal symptoms have already passed, and some drugs don't have severe withdrawal symptoms
* detoxified users can still remain addicted
* treatments used to curb withdrawal are not 100% effective
* but, some emotional effects of drug withdrawal (depressed mood) may persist for some time after physical withdrawal symptoms have ceased- this may contribute to persistence of addiction
48
what is the positive reward model (theory of drug addiction) and what are some problems with it?
those with substance use disorders take drugs for the pleasurable feelings, some feel more of a positive feeling from the same drug
*problems: people with substance use disorders may continue to seek drugs even if they are no longer given a good rush
* tolerance to hedonic effects develops
* some drugs (nicotine) do not give as much of a euphoric rush as other drugs (heroin) but can be just as addictive
49
what happens when we reduce DA transmission in animal models with self-stimulation?
* reducing DA transmission reduces/abolishes self administration for most drugs (except opioids)
* blocking DA receptors also disrupts formation of conditioned place preference for drugs
50
how does the body respond to drugs vs. natural rewards?
* responding for drugs of abuse, AND consumption of natural rewards or reward-associated cues are associated with increase in DA release in the accumbens
* magnitude of DA release by drugs of abuse can be greater/prolonged than that induced by natural rewards
* so, drugs of abuse activate the brain's natural reward learning pathways, but to a much greater degree
51
if drugs increase pleasure and dopamine, does dopamine = pleasure?
* no, reward has 2 components
1. “liking” = pleasurable, hedonic effects of rewards
2. “wanting” = craving, willingness to work for rewards
* dopamine increases when we feel good, but it is not the reason that we feel pleasure
52
does blocking dopamine receptors in humans alter ratings of drug euphoria? why or why not?
* blocking dopamine receptors in humans does not alter subjective ratings of drug euphoria
* dopamine is not involved in the pleasurable effects of drugs of abuse (or natural rewards)
* dopamine is more involved in the preparatory/approach behaviours associated with rewards and conditioned stimuli
* endogenous opioids (endorphins) play a role in pleasurable aspects of rewards
* so, dopamine helps get you to the good things in life (wanting), but doesn’t seem to be involved in you liking them
53
how does pavlovian conditioning show DA's connection to reward-related stimuli?
* cue comes on, predicts food delivery 5 s later regardless of whether animal interacts with lever
* animals start to approach/press/bite lever (where the cue is) while waiting for food delivery
* cue evokes DA release, associated with approach behaviour (getting close to the stimulus that predicts reward, not the reward itself)
* DA increases again when reward delivered
* blocking NAc DA receptors reduces approach to cue (but DOES NOT disrupt approach/consumption of food reward)
so, dopamine promotes behaviors directed towards reward-related stimuli
54
what happens to the dopamine system with repeated exposure to addictive drugs?
* repeated exposure to all drugs with a high addictive potential (like cocaine) can induce sensitization of DA release
* sensitization: repeated DA exposure results in more of an increase in locomotor activity than if you just had one dose of amphetamine
* makes dopamine system more sensitive, more DA release to the same stimuli/drug
* also enhances DA release to reward-cues
* studies in humans have shown these effects can be long lasting (DA response still sensitized a year later)
so, repeated drug exposure can put you into a hyperdopamine state which can lead to sensitized DA release in response to cues associated with drug
55
how does dopamine affect conditioned reinforcement?
1. CS light comes on and then reward is presented
2. Levers are inserted into chamber (one lever gives CS light, other gives nothing)
* animals will press lever just for the CS, even though lever press never gives reward
* reward-associated cue is now reinforcing, animals will work for it
* give amphetamine (increase DA release) rats responds much more for conditioned reinforcer
* Important point: rats sensitized to drugs like cocaine respond more for conditioned reinforcement even when tested drug-free weeks after treatment (effects persist)
so, in a hyperdopamine state, the cues exert much more powerful influence over behaviour
56
how can the reinstatement of drug seeking be modeled in animals? what does this tell us about triggers and drug relapse?
* relapse of drug taking after abstinence can be modeled in animals with a "reinstatement" paradigm
1. train animals to administer drug (cues can be presented with drug infusion)
2. take rat through extinction (lever press no longer delivers drug or cues, rat eventually stops responding)
3. on test day, lever pressing still provides no drug, but reinstatement of lever pressing can be induced by...
* a drug prime, a stressor (foot-shock) or drug associated cues
* each of these triggers evokes DA release in the accumbens
* blocking DA transmission reduces all types of reinstatement of drug-seeking
so, a drug "taste" cue associated with the drug, or stress can
1. Increase accumbens DA release and
2. Trigger drug-seeking behaviour
57
what is the incentive-sensitization hypothesis?
the idea that cues associated with drug-taking take over behaviour
* initial drug taking is driven by pleasurable effects
* over time, tolerance develops to hedonic effects (liking the drugs less) but effects on DA system and impact on how drug-related cues influence drug-seeking become sensitized
* drug-related cues activate neural networks (including DA system) that trigger unconscious conditioned responses that may be viewed as craving (make you THINK you WANT the drug)
* associative memories between the effects of the drug and associated cues become amplified by the hyperdopaminergic state
* drug cues trigger more craving and then more drug taking, even if the effects of the drug are not as pleasurable
