Lec 43 Addiction Flashcards

1
Q

What is intoxication?

A

substance-specific acute syndromes associated with impaired function

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2
Q

What is tolerance?

A

reduced effect of a drug given at a constant dose [need escalating dose to get same effect]

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3
Q

What is sensitization?

A

reverse of tolerance –> increasing drug effect at constant dose

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4
Q

What is dependence?

A

altered psychological state induced by repeated exposure to a drug

–> shows withdrawal symptoms when drug is discontinued

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5
Q

What is addiction?

A
  • compulsive seeking and taking of drug despite adverse consequences
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6
Q

What is craving?

A

intense urges to take a drug

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7
Q

What is relapse?

A

return to drug abuse after period of abstinence

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8
Q

What are the CAGE screening questions for alcohol?

A
  • thought about cutting down
  • annoyed when others criticized
  • felt guilty
  • eye opener
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9
Q

What are the AUDIT-C screening questions?

A
  • how often do you have a drink containing alcohol
  • how may standard drinks containg alcohol do you have on a typical day
  • how often do you have six or more drinks on one occasion
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10
Q

What is reward?

A

positive emotional effects

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11
Q

What is reinforcement?

A

stimulus that causes reponse to be maintained and increased

positive –> increase behavior to get positive reward
negative –> increase behavior to end punishment

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12
Q

What is the most important brain reward circuit

A

the mesolimbic dopamine system

DA neurons in VTA of midbrain –> nucleus accumbens [in ventral striatum of limbic forebrain]

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13
Q

What is activity of VTA dopamine neurons from reward, from expectation of reward, from absence of expected reward, vs from unexpected reward?

A

reward: activates VTA

expectation of reward: activates VTA

absence of expected reward: inhibits VTA neurons

unexpected reward: activates neurons even more than any of the others

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14
Q

What is effect of drugs of abuse on mesolimbic dopamine path?

A
  • they activate VTA-nuc accumbens
  • with repeated exposure, cause changes in circuit that dampen its sensitivty –> natural rewards no longer able to activate VTA neurons, only the drug of absue powerful enough to produce effect

—-> thus pt only feels normal when drug is on board

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15
Q

What is role of hippocampus in drug addiction?

A
  • involved in drug-related memories
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16
Q

What is role of amygdala in drug addiction?

A
  • normally: establishes association between environmental cues and negative emotional experience = fear conditioning
  • with drugs: establishes association between environmental cues and positive emotional experience of drug use
17
Q

What is the role of frontal cortical regions in drug addiction?

A
  • each area functionally connected to VTA- nucleus accumbens circuit
  • their function = attention, working memory, planning, impulsivity
18
Q

What is hypofrontality?

A
  • addiction is associated with hypofunction of frontal cortical regions –> increased impulsivity and compulsivity
19
Q

Which 3 drugs mimic neurotransmitters by activating receptors?

A
  • morphine
  • nicotine
  • marijuana
20
Q

What 2 drugs block the dopamine pump?

A
  • cocaine

- amphetamine

21
Q

What 3 drugs activate or inhibit channels?

A
  • alcohol
  • PCP
  • ketamine
22
Q

What is action of opiates?

A
  • opioid receptor agonists [primarily mu]
  • mimic enkephalins/endorphins/dynorphins
  • inhibit inhibitory GABA neurons in VTA –> more activation of VTA DA neurons

effects: analgesia, euphoria, sedation, constipation, respiratory depression
- physical dependence and tolerance to analgesic effect can be independent from

receptor signaling = Gi

23
Q

What is action of cocaine?

A
  • blocks monamine reuptake inhibitor –> increased effect of DA [and 5HT, NE] transmission
  • inhibition of DA reuptake at nucleus accumbens nerve terminals = more reward action

effects: euphoria, increased arousal/self-cofidence, decreased fatigue/appetite

repeated chronic use –> tolerance of positive effects, sensitization of adverse effects

receptor signalling = Gi and Gs

24
Q

What can be used to treat opiate overdose?

A
  • opioid receptor antagonists = naloxone, naltrexone
25
Q

What is action of amphetamines [amphetamine/ methamphetamine/ ritalin[methylphenidate]]?

A
  • bind to DAT [dopamine transporter] –> pumps more DA [and 5HT, NE] into the synapse –> increased effect of DA transmission
  • increase DA in nucleus accumbens
    effects: euphoria, increased arousal/self-confidence, decreased fatigue/appetite

repeated chronic use –> tolerance of positive effects, sensitization of adverse effects

receptor signalling = Gi and Gs

26
Q

What is action of nicotine?

A
  • agonist at nicotinic ACh ligand-gated channel receptors
  • directly activates VTA DA neurons or acts via glutamate nerve terminals [that normally activate DA neurons]

effects: mild euphoria, increased alertness, muscle relaxation, analgesia, nause

27
Q

What is action of PCP?

A
  • non-competitive antagonist of NMDA ligand-gated glutamate receptor
  • inhibits glutamate inputs to nucleus accumbens –> same net functional effect as activation of DA/opioid receptors
    effect: psychotic state similar to schizophrenia
28
Q

What is action of alcohol?

A
  • acts only at very high conc = low affinity for binding sites in the brain
  • diffuse action, not well characterized
  • acts first on GABA-A receptors –> then NMDA –> then voltage-gated channels
  • activate GABA-A = anxiolytic/sedative
  • inhibit NMDA-R: dissociative, psychotic effects
  • inhibit voltage-gate ion channels: coma, death
29
Q

What brain adaptations underly addiction

A
  • neuroplastic changes
  • hypofrontality
  • altered gene expression
30
Q

What neuroplastic changes occur with drug use?

A
  • changes in reward (VTA-NAc) and learning (hippocampus, amygdala, PFC) circuits
  • synaptic + electro adaptations persist for years, trigger sensitization, tolerance, craving, relapse, reduced response to natural reward
31
Q

What is the mech of cAMP path alteration in presence of chronic opiate exposure?

A
  • opiate initially inhibits cAMP synthesis by stimulating Gi
  • with repeat exposure –> cell undergoes homeostatic response to upregulate CREB [camp response element binding protein] –> increased synthesis adenylyl cyclase and PKA
  • -> increase capacity of cAMP path –> opposes opiate inhibition = tolerance

when drug discontinued –> cAMP continues to be upregulated and now unopposed = abnormal activity in cell after absence of drug = dependence/withdrawal

32
Q

Is addiction genetic?

A

50% of risk is genetic –> no specific genes identified

33
Q

What is methadone?

A

mu opioid receptor agonist = prodrug of morphine with long half life, allows for no withdrawal and less of a high

34
Q

What is analogous to methadone but for nicotine addiction treatment?

A

nicotine patch or chewing gum

35
Q

What is burprenorphine?

A

partial opioid agonist

thus causes enough agonist to satisfy drug craving but taking more buprenorphine will not cause high

36
Q

What is varenicline?

A
  • new treatment for nicotine addiction
  • partial agonist at nicotinic cholineragic receptors [target of nicotine]
  • like buprenorphine but for nicotine
37
Q

What is naltrexone?

A

opioid receptor blocker
prevents ability of opiates to produce their effects
can also be used for alcohol and nicotine addiction

38
Q

What are CB1 antagonists [eg rimonabant]?

A
  • used for cannabinoid addiction
39
Q

What is acamprosate?

A
  • used for alcohol addiction

- reduces glutamatergic function