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PMCOL 305 > Midterm 1 > Flashcards

Midterm 1 Flashcards

1
Q

Cocaine withdrawal often has ____ physical symptoms but ___ psychological ones

A

Cocaine withdrawal often has no physical symptoms but intense psychological ones

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2
Q

With withdrawal long-term DAT efficiency ____, may explain ____ ___ episodes

A

With withdrawal long-term DAT efficiency increases, may explain common depressive episodes

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3
Q

Withdrawal symptoms include…

A

depression, anxiety, appetite changes

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4
Q

Intermittent use of cocaine associated with strong behavioural sensitization, ___ locomotor activity

A

Intermittent use of cocaine associated with strong behavioural sensitization, increased locomotor activity

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5
Q

Reverse tolerance

A

Increased susceptibility to hyperthermia, convulsions, stereotyped movements

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6
Q

Altered opioid-ergic signaling → ___ ____ expression is induced (generated)

A

Altered opioid-ergic signaling → striatal dynorphin expression is induced

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7
Q

When there is reduced euphoria by cocaine that is because ___ DA and ___ DAT efficiency

A

When there is reduced euphoria by cocaine that is because depleted DA and increased DAT efficiency

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8
Q

After cocaine binds the same site as dopamine it locks transporter in ___ conformation which ___ the transporter

A

After cocaine binds the same site as dopamine it locks transporter in stable conformation which inactivates the transporter

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9
Q

cocaine binds ___ ___ as dopamine

A

cocaine binds same site as dopamine

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10
Q

___ % of cocaine users combine their use with alcohol, this causes ___ ____ leading to the byproduct ____ being produced which is a potent ____

A

30-60 % of cocaine users combine their use with alcohol, this causes altered metabolism leading to the byproduct cocaethylene being produced which is a potent vasoconstrictor

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11
Q

cocaine causes ___ acute infections in GI tract which leads to ___ blood flow causing ____ ___ ___

A

cocaine causes increased acute infections in GI tract which leads to reduced blood flow causing tissues to die

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12
Q

Another adverse effect of cocaine use include formication which is …

A

the delusion of crawling insects under skin

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13
Q

Some adverse affects of acute cocaine use include irritability, ____, ____, ___ and ___

A

Some adverse affects of acute cocaine use include irritability, hostility, anxiety, fear and restlessness

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14
Q

After cocaine use NE excess underlies ___ effects, which enhances ___ sensitivity to ___ and ___

A

After cocaine use NE excess underlies sympathomimetic effects, which enhances VTA sensitivity to Glu and reward

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15
Q

After cocaine use 5HT excess underlies ___, ____,____ and __

A

After cocaine use 5HT excess underlies mood, sleep ,appetite and temperature

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16
Q

After cocaine use DA is in ___ in the ____, ___, ____ and ___

A

After cocaine use DA is in excess in the basal ganglia, PFC, VTA and NAc

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17
Q

The neurotransmitters affected by cocaine are

A

NE, DA, 5HT

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18
Q

The ____ and ____ of cocaine mimics NTs

A

The aromatic ring and amine group of cocaine mimics NTs

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19
Q

A high dose of cocaine can affect the medulla which in turn can lead to..

A

respiratory and circulatory failure

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20
Q

Cocaine’s effects on NAc make it

A

extremely rewarding

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21
Q

Cocaine effects on the PFC

A

influences planning, problem-solving and social behaviours

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22
Q

___ onset= ___ euphoria

A

faster onset= greater euphoria

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23
Q

cocaine causes ___ movements

A

cocaine causes repetitive, compulsive movements

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24
Q

Because of the excess neurotransmitters : ___, ___, ___ and ___ cocaine causes sympathomimetic effects like ___ heart rate, ___ blood pressure, ____, ____, ____ and ___

A

Because of the excess neurotransmitters : dopamine, serotonin, norepinephrine and epinephrine cocaine causes sympathomimetic effects like increased heart rate, increased blood pressure, anorexia, insomnia, agitation and hyperthermia

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25
Q

The anaesthetic effects of cocaine in the heart causes ____

A

The anaesthetic effects of cocaine in the heart causes dysrhythmias

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26
Q

cocaine is an anaesthetic as it blocks ___ channels which blocks ____ leading to no pain

A

cocaine is an anaesthetic as it blocks Na channels which blocks neuotransmission leading to no pain

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27
Q

Cocaine can be detected in the urine ___ days and __ ___ in chronic users

A

Cocaine can be detected in the urine 4 days and 2 weeks in chronic users

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28
Q

When an individual uses alcohol and cocaine at the same time, ____ develops in the liver

A

When an individual uses alcohol and cocaine at the same time, cocaethylene metabolite develops in the liver

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29
Q

Liver/plasma esterases generate ___ ___ which is a marker for crack cocaine use

A

Liver/plasma esterases generate ecogonine methylester which is a marker for crack cocaine use

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30
Q

Major metabolite of cocaine is benzoylecgonine → 40% is
spontaneously____ by ____ within ___ hours of use

A

Major metabolite of cocaine is benzoylecgonine →40% is spontaneously produced by hydrolysis within 4 hours of use

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31
Q

___ is an enzyme that is mainly located in the liver and controls the metabolism of cocaine

A

CYP3A4

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32
Q

3 main consumable forms of cocaine

A

1) Coca leaves
2) Cocaine hydrochloride
3) Free-base cocaine= crack

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33
Q

Half-life

A

time to remove 50% of the concentration of drug from circulation

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34
Q

Drug half-lives indicate ____

A

Drug half-lives indicate how long the drug remains in circulation

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35
Q

bioavailability of ingestion

A

5-99%

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36
Q

duration of ingestion

A

6+ hrs

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37
Q

onset of ingestion

A

20-45 min

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38
Q

insufflation has ____ pathway to the BBB

A

insufflation has long pathway to the BBB

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39
Q

bioavailability for insufflation

A

up to 80%

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40
Q

duration of insufflation/snorting

A

5-8 hr

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41
Q

onset for insufflation/snorting

A

10-45 min

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42
Q

routes of administration with first-pass metabolism

A

ingestion

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43
Q

routes of administration with no first-pass metabolism…

A

injection and insufflation

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44
Q

Routes of administration

A

inhalation, injection, insufflation, ingestion

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45
Q

Injection has ___ circulatory path to brain from ___ –> ___–> left side of heart –> ___

A

Injection has 2nd shortest circulatory path to brain from right side of heart –> lungs–> left side of heart –> BBB

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46
Q

Duration for injection

A

2-4 hr

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47
Q

onset for injection

A

10-20 seconds

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48
Q

____ has shortest circulatory path to brain from ___ –> ___ –> _____

A

inhalation has shortest circulatory path to brain from lungs –> left side of heart –> BBB

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49
Q

Bioavailability of inhalation

A

5-99%

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50
Q

Duration of inhalation

A

2-4 hr

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51
Q

Onset of inhalation

A

7-10 seconds

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52
Q

Bioavailability is…

A

the amount of administered drug reaching systemic circulation i.e. unchanged

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53
Q

Slower absorption routes:
- ____ peak
- correlate with ___ ____ reported high
- ____ duration in the brain

A

Slower absorption routes:
- lower peak
- correlate with less intense reported high
- prolonged duration in the brain

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54
Q

Faster absorption routes= ___ delivery to the brain:
- ___peak
-correlate with ___ reported high
- drug ___ ____ remain in brain very long

A

Faster absorption routes= faster delivery to the brain:
- higher peak
-correlate with stronger reported high
- drug does not remain in brain very long

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55
Q

Predispositions

A

A tendency/vulnerability to suffer from a particular condition

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56
Q

Polygenicity

A

multiple genes are involved in addiction

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57
Q

___ D2/D3 receptor expression in NAc of drug- naïve high- impulsive rats

A

Reduced D2/D3 receptor expression in NAc of drug- naïve high- impulsive rats

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58
Q

High impulsive rats display ___ cocaine self- administration

A

High impulsive rats display greater cocaine self- administration

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59
Q

Submissive monkeys display ___ D2 receptor levels and ___ vulnerability to cocaine self-administration

A

Submissive monkeys display lower D2 receptor levels and higher vulnerability to cocaine self-administration

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60
Q

D2 level differences are ___ in socially- housed monkeys

A

D2 level differences are amplified in socially- housed monkeys

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61
Q

In humans, individual characteristics predict high vulnerability to drug addiction, these include:

A

• sensation- and novelty-seeking
• trait impulsivity
• anti-social conduct disorder (especially in
adolescence)

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62
Q

In animal models, individual characteristics that predict high vulnerability to drug-seeking behaviour include…

A

• high reactivity to stress
• high novelty-induced locomotor activity
• high novelty-seeking
• high trait impulsivity

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63
Q

Subjects with deficits in striatal D2 levels report a ___ experience with methylphenidate

A

Subjects with deficits in striatal D2 levels report a pleasurable experience with methylphenidate

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64
Q

Healthy male subjects with robust striatal DA levels report ___ experience with methylphenidate

A

Healthy male subjects with robust striatal DA levels report displeasurable experience with methylphenidate

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65
Q

Causes of reward deficiency hypothesis

A

1) Deficiency of D2 receptors in the reward circuit
2) An aberration in D3 receptors in the reward circuit
3)Due to a deficiency in presynaptic DA levels in the NAc

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66
Q

Adoption studies→more likely to display ___ family than ____ family habits

A

Adoption studies→more likely to display birth family than adopted family habits

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67
Q

Twin studies→ ____ twins have more similar rates of addiction than ____ twins

A

Twin studies→ monozygotic twins have more similar rates of addiction than heterozygotic twins

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68
Q

All drugs are ___ – ____

A

All drugs are pleiotropic – cause multiple physiological effects

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69
Q

ACh activates ___ responses, plays a major role in ____ and ___

A

ACh activates parasympathetic responses, plays a major role in learning and memory circuits

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70
Q

Generally, drugs that target 5HT receptors are ___

A

Generally,drugs that target 5HT receptors are less addictive

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71
Q

NE plays a major role in ___

A

NE plays a major role in stress-induced drug relapse

72
Q

NE innervation activates ___ responses

A

NE innervation activates sympathetic responses

73
Q

Lab animals prefer ___ over ___, ____, ___ and ___ even in the presence of aversive and painful consequences

A

Lab animals prefer drugs over food, water, toys and sex even in the presence of aversive and painful consequences

74
Q

In the context of addictive drugs, the learning signal leads to drug ___ behaviours leading to ___ drug intake at the expense of all other behaviours

A

In the context of addictive drugs, the learning signal leads to drug adaptive behaviours leading to compulsive drug intake at the expense of all other behaviours

75
Q

Once the reward becomes fully predictable, DA- ergic neurons ____ and learning ____

A

Once the reward becomes fully predictable, DA- ergic neurons are no longer triggered and learning ceases

76
Q

Phasic firing of VTA DA-ergic neurons generates a ____ signal when an ____ reward occurs

A

Phasic firing of VTA DA-ergic neurons generates a learning signal when an unexpected reward occurs

77
Q

NMDAR expressed in ___

A

NMDAR expressed in hippocampus

78
Q

mGluR7 is expressed in ___, ___, ___

A

mGluR7 is expressed in Hippocampus, Amygdala, locus coeruleus

79
Q

mGluR3 is expressed in ___

A

mGluR3 is expressed in NAc

80
Q

____ – potentiation last minutes, weeks, months; unique to LTP

A

Persistence – potentiation last minutes, weeks, months; unique to LTP

81
Q

___ – many weak stimuli can induce LTP; constructive interference

A

Cooperativity – many weak stimuli can induce LTP; constructive interference

82
Q

___ – sites of LTP are confined to specific contact sites

A

Specificity – sites of LTP are confined to specific contact sites

83
Q

LTP = ___ of synaptic transmission between two neurons ___ of glutamate receptors

A

LTP = strengthening of synaptic transmission between two neurons downstream of glutamate receptors

84
Q

Group I Gq-linked – ____
excitotoxicity risk

A

Group I Gq-linked – increase
excitotoxicity risk

85
Q

Glutamate receptors (mGlu-R) are involved in__

A

synaptic plasticity

86
Q

NMDAR has ___ signalling

A

Ca2+ (calcium)-dependent

87
Q

NMDAR is critical for ___

A

NMDAR is critical for synaptic plasticity (LTP/LTD)

88
Q

NMDAR is co-activated by ___ and ___

A

NMDAR is co-activated by glutamate and Serine/Glycine

89
Q

NMDAR is ___

A

ionotropic

90
Q

AMPAR has a major role in ___

A

long-term depression (LTD)

91
Q

AMPAR is ___ and forms __

A

AMPAR is ionotropic and forms tetramers

92
Q

Hedonic dopamine tone is reduced during ___, causing___

A

Hedonic dopamine tone is reduced during withdrawal, causing dysphoric state

93
Q

After drugs wear off, addicts experience ____ and ____ within this circuit leading to ___

A

After drugs wear off, addicts experience post-use dysphoria and depressed activity within this circuit leading to further drug use to avoid unpleasant feelings

94
Q

Tolerance to some drugs leads to ___ of hedonic tone (___ euphoria) during chronic use causing addicts to use ___ doses to ____

A

Tolerance to some drugs leads to lowered elevation of hedonic tone (lowered euphoria) during chronic use causing addicts to use higher and higher doses to restore homeostatic dopamine levels to ‘get straight

95
Q

Antagonists produce subjectively ___ effects in humans,___ of drug-taking behaviours

A

Antagonists produce subjectively aversive effects in humans, extinction of drug- taking behaviours

96
Q

Dopamine antagonists are __ reinforcers that enhance behaviours to ___

A

Dopamine antagonists are negative reinforcers that enhance behaviours to reduce administration

97
Q

Intracerebral microinjections of nicotine produce ___ and ___

A

Intracerebral microinjections of nicotine produce conditioned place preference and voluntary self-administration

98
Q

All addictive drugs cause lab animals to ___and enhance ___

A

All addictive drugs cause lab animals to self- administer frequently and enhance functioning of the reward circuitry

99
Q

Dopamine is the neurotransmitter of __

A

Dopamine is the neurotransmitter of reward

100
Q

Addictive drugs induce ___ firing in the __

A

Addictive drugs induce phasic DA firing in the NAc

101
Q

You can measure neurotransmitter levels in specific nuclei directly via ___

A

You can measure neurotransmitter levels in specific nuclei directly via microdialysis

102
Q

___ (CPP) is when pairing an __ with stimulation of ___projections causes ____that persists for several days

A

Conditioned place preference (CPP) is when pairing an environment with stimulation of VTA DA-ergic projections causes immediate place preference that persists for several days

103
Q

Effort exerted to self-administer is related to _____

A

Effort exerted to self-administer is related to degree of reward experienced

104
Q

Self-administration in animal studies is via ___, e.g. __, __

A

Self-administration in animal studies is via instrumental behaviour, e.g. lever-press, nose poke

105
Q

Animal tests assess ___ of a drug and ___

A

Animal tests assess addictiveness of a drug and translate well to humans

106
Q

D2-like type ___ cytoplasmic (cAMP) via adenylyl cyclase

A

decreases

107
Q

D2-like type are couple to ___

A

Giα

108
Q

D2-like type are ___

A

D2, D3 and D4

109
Q

D1-like type (D1 and D5) ___ cytoplasmic (cAMP) via adenylyl cyclase

A

increases

110
Q

D1-like type (D1 and D5) receptors are coupled to __

A

Gsα

111
Q

There are __ dopamine genes which are ___ that encode for __ dopamine receptors (DRs) which are ___

A

There are 5 dopamine genes which are DRD1-DRD5 that encode for 5 dopamine receptors (DRs) which are D1-D5

112
Q

There is a link between low 5-HT and ___ and ____

A

There is a link between low 5-HT and impulsivity and violence in addicts

113
Q

__ is the major source of serotonin

A

raphe nuclei

114
Q

5-HT (seretonin) is a ___

A

monoamine indole

115
Q

___receptors are involved in LTD and LTP

A

glutamate

116
Q

Glu has a major role in ___

A

Glu has a major role in cue-triggered relapse

117
Q

Glu (glutamate) is an ___

A

amino acid

118
Q

ACh is central to ____

A

ACh is central to learning/memory

119
Q

the major inhibitory neurotransmitter is ___

A

GABA

120
Q

NE has a big role in ____

A

NE has a big role in stress-induced relapse

121
Q

Major source of NE projections in the brain come from the ___

A

Major source of NE projections in the brain come from the locus coeruleus

122
Q

NE (norepinephrine) is a ___

A

catecholamine

123
Q

DA is the primary ____in particular during the ____phase

A

DA is the primary driver of reward circuit in particular during the VTA→NAc 2nd phase

124
Q

Dopamine (DA) is a __

A

catecholamine

125
Q

Withdrawal is the generally ___ affective ___ and ___ due to ____/___

A

withdrawal is the generally unpleasant affective mood and symptoms due to tolerance/dependence

126
Q

Tolerance is taking ___ drug __ feeling effects or needing ___

A

Tolerance is taking more drug without feeling effects or needing more drug to feel the same effect

127
Q

The change from __-driven to ____-driven drug-seeking behaviour correlates with a ____ ___ mediated shift in control of ____ behaviour

A

The change from reward-driven to goal-driven drug-seeking behaviour correlates with a ventral striatum-to-dorsal striatum- mediated shift in control of drug-seeking behavior

128
Q

Addiction starts as ___use then ___ use then ____ use

A

Addiction starts as occasional recreational use then impulsive use then habitual compulsive use

129
Q

____ and ___ are critical neurotransmitters

A

Dopamine and glutamate are critical neurotransmitters

130
Q

When dendrites or soma reach threshold, nerve
fires = ____

A

When dendrites or soma reach threshold ,nerve
fires = action potential

131
Q

An ability to form new connections, change wiring patterns and establish new pathways = ____

A

An ability to form new connections, change wiring patterns and establish new pathways = neural re-wiring

132
Q

Amygdala inputs are at the core of ___/___ circuits

A

Amy inputs are at the core of reinstatement/relapse circuits

133
Q

Frontal inputs are at the core of ___, e.g. PFC

A

Frontal inputs are at the core of anticipation circuits, e.g. PFC

134
Q

Many addictive drugs lose their ___ effect

A

Many addictive drugs lose their euphoric effect

135
Q

VTA→NAc DA-ergic projections are at the core of ____

A

VTA→NAc DA-ergic projections are at the core of the reward circuit

136
Q

All drugs of abuse elevate ___which reinforces drug-___ behaviours

A

All drugs of abuse elevate striatal dopamine which reinforces drug-taking behaviours

137
Q

Repeated administration of addictive drugs can lead to ____ drug-seeking behaviour

A

Repeated administration of addictive drugs can lead to compulsive drug-seeking behaviour

138
Q

Compulsivity results in decreased ___ over ___, diminished ability to ____ or ___ _____ behaviours and a tendency to perform ____ in a ___ or ____ manner

A

Compulsivity results in decreased voluntary control over urges, diminished ability to delay or inhibit compulsive behaviours and a tendency to perform repetitive acts in a habitual or stereotyped manner

139
Q

Compulsivity refers to a tendency toward ___, ___, repeated despite ___

A

Compulsivity refers to a tendency toward repetitive, habitual actions, repeated despite adverse consequences

140
Q

Impulsivity results in ___ and ___ before acting

A

Impulsivity results in reduced thought and judgement before acting

141
Q

___activity is mainly involved in impulsivity

A

Dorsolateral prefrontal activity is mainly involved in impulsivity

142
Q

Deficient __ cognitive control- an inability to ___

A

Deficient frontostriatal “top-down” cognitive control- an inability to override thoughts that lead to actions

143
Q

Measures of impulsivity rely on__, ___and ___

A

Measures of impulsivity rely on self-reports, behavioural scores and electrophysiology

144
Q

Initially, drug-taking behaviour is ___

A

Initially, drug-taking behaviour is reward-driven

145
Q

__→__ projections have implicated __ in neuropsychiatric disorders; OCD, ADHD, schizophrenia and others

A
146
Q

RN projects to ____, ___, ___ and ___

A

RN projects to hypothalamus, limbic system, brainstem and spine

147
Q

RN (raphe nuclei) regulate __, __, ___, ___, __, __, ___, ___ and ___

A

RN (raphe nuclei) regulate mood, emotion, aggression, sleep, anxiety, memory, appetite, pain and temperature

148
Q

RC is located in

A

the dorsal medulla oblongata, multiple nuclei

149
Q

LC projects to __, __, ___, ___, __, ___, ____,
___, ___ and __

A

LC projects to VTA, brainstem, cerebellum,
thalamus, hypothalamus, hippo, Amy,
basal ganglia, cortex and spine

150
Q

LC (locus coeruleus) regulates ___, ___, ___, ___, ___, ___, ___

A

LC regulates arousal, cognition, memory,
sleep-wake, attention, emotion, stress

151
Q

Locus coeruleus (LC) is located in __

A

the dorsal pons

152
Q

VTA has reciprocal projections with _, _, _, _, basal ganglia and others

A

VTA has reciprocal projections with NAc, Amy, RN, PFC, basal ganglia and others

153
Q

Drugs accumulate in the ___ binding to the transporters

A

Drugs accumulate in the CN, binding to the transporters

154
Q

CN has reciprocal connections with ___, ___, ___, ___

A

CN has reciprocal connections with VTA, NAc, Hippo, Amy

155
Q

CN is involved in ___, ___, ____, ___, ___, ___

A

CN is involved in voluntary movement, learning, memory, sleep, pain, social behaviour

156
Q

Basolateral amygdala permits ___, ____by medial PFC

A

Basolateral amygdala permits emotional regulation, decision making by medial PFC

157
Q

Chronic drug abuse disrupts ___ →____connections

A

Chronic drug abuse disrupts Amy →PFC connections

158
Q

Amygdala associates cues with ____, ___, ____

A

Amygdala associates cues with drug consumption, conditioning, reinstatement

159
Q

Amygdala has key involvement in ____, most disabling symptom in addicts

A

Amygdala has key involvement in emotional reactivity, most disabling symptom in addicts

160
Q

Amygdala has role in ___, ___, ____, ____, ___, __, ____

A

Amygdala has role in emotions (fear, pleasure), learning, memory, reward, attention, arousal, stress

161
Q

VTA→____ projections modulate plasticity and learning/memory

A

VTA→Hippo projections modulate plasticity and learning/memory

162
Q

Hippocampus contains___ cells, ____ by drugs of abuse

A

Hippocampus contains neuronal stem cells, suppressed by drugs of abuse

163
Q

Hippocampus has role in __, ____and ____ information

A

Hippocampus has role in memory formation, processing novel and contextual information

164
Q

Location of hippocampus

A

para-saggital plane, caudal amygdala

165
Q

PFC has reciprocal connections with multiple regions involved with ___, ___, ___

A

PFC has reciprocal connections with multiple regions involved with attention, action, cognition

166
Q

PFC → ___ + ___ expression of behaviours trained by chronic drug abuse

A

PFC → VTA + Amygdala expression of behaviours trained by chronic drug abuse

167
Q

PFC has role in ___, __, ___, ___, ___, ___, ___, ____, ____

A

PFC has role in self-awareness, planning, problem solving, learning, memory, executive functions, personality, decision making, social behaviour

168
Q

PFC is located in the

A

frontal lobe and extends into medial regions

169
Q

VTA is the main driver of _

A

VTA is the main driver of rewarding feelings

170
Q

VTA is involved in _, _, _

A

VTA is involved in cognition, motivation, locomotor activity

171
Q

VTA is located in the _

A

midbrain

172
Q

NAc has reciprocal projections with _, _, _, _, _

A

NAc has reciprocal projections with VTA, PFC, Amy, Hippo, basal ganglia

173
Q

NAc is the __ centre, involved in _ , cognitive processing of __, ___ of drug-taking, translating emotional stimulus into __

A

NAc is the pleasure centre, involved in motivation, cognitive processing of aversion, reward/reinforcement of drug-taking, translating emotional stimulus into behaviour/action

174
Q

Nucleus accumbens (NAc) location

A

basal forebrain striatum

175
Q

PFC has reciprocal connections with multiple regions involved with ___, ___, ___

A

PFC has reciprocal connections with multiple regions involved with attention, action, cognition

PMCOL 305 (3 decks)

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