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Neuropharmacology > Chapter 9: Drug Abuse And Addiction > Flashcards

Chapter 9: Drug Abuse And Addiction Flashcards

1
Q

What is addiction?

A

Addiction is a collection of behaviors
- compulsive drug seeking and drug using behaviors

Characterized by a chronic tendency to relapse
- periods of abstinence interrupted by drug use

  • Chronic, relapsing behaviored disorder
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2
Q

Drug Abuse

A

Problematic drug use that might meet DSM-5 criteria for mild/ moderate substance use disorder

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3
Q

Addiction

A

Problematic drug use that might meet DSM-5 criteria for severe substance use disorder

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4
Q

Addiction is characterized by a […] tendency to […]

A

Addiction is characterized by a chronic tendency to relapse

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5
Q

Behavioral aspects of addiction

A
  • compulsive drug-seeking and drug-using behavior

- Cravings- strong urges to take the drug

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6
Q

Chronic, relapsing aspect of addiction

A
  • long-lasting

- drug-free periods followed by relapse to drug use

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7
Q

Impulsive Stage of Addiction

A
  1. Binge intoxication
  2. Pleasurable effects
  3. Abstinence; Neural affect
  4. Reward craving
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8
Q

Compulsive Stage of Addiction

A
  1. Prolonged intoxication
  2. Relief
  3. Prolonged abstinence/ Negative affect
  4. Relief craving
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9
Q

DSM-5 drug classes

A
  1. Alcohol
  2. Caffeine
  3. Cannabis
  4. Hallucinogens
  5. Inhalants
  6. Opioids
  7. Sedative-hypnotic and anxiolytics drugs
  8. Stimulants
  9. Tobacco
  10. Others
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10
Q

Substance Use Disorders

A

A pattern of use that is “problematic,” leading to “significant impairment and distress”

*continues using substance despite significant substance-related problem

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11
Q

Substance-induced disorders

A

Substance-specific syndromes due to recent substance use

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12
Q

Addiction potential of a substance is influenced by route of administration

A

IV and inhalation (greatest abuse potential)

  • Rapid absorption, fast onset, short duration
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13
Q

Drugs of abuse share 2 important properties

A

Positively reinforcing

Rewarding

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14
Q

Positive reinforcing

A
  • consuming the drug strengthens whatever preceding behavior was performed
  • how hard an animal will work for a drug
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15
Q

Rewarding

A
  • the positive experience associated with the drug

- the “high” and feeling of relaxation

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16
Q

Tool for studying positive reinforcement

A

Drug self-administration

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17
Q

How hard will an animal work for drugs?

A
  • drug response (continuous reinforcement (fixed ratio))
    - after certain point, drug starts to interrupt behavior
    - drug satiation, aversive reactions, behavioral disruptive side effects
  • Discriminative stimulus also contribute to drug-seeking behavior

Breaking point- response ratio at which responding ceases

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18
Q

Rewarding properties if drugs are commonly evaluated using

A

Place conditioning
- animals conditioned to associate a particular chamber with morphine show preference for that chamber

Electrical self-stimulation

   - drugs of abuse sometimes have aversive effects
   - drugs of abuse decrease electrical self-stimulation
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19
Q

Withdrawal from ethanol […] threshold for electrical self-stimulation of reward pathway

A

Withdrawal from ethanol increase threshold for electrical self-stimulation of reward pathway

  • reinforcement is less rewarding that it was during initial ethanol use
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20
Q

Natural recovery

A

Abstinence with little to no treatment

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21
Q

Relapse to drug use is modeled by […]

A

Relapse to drug use is modeled by reinstatement

  • Forced abstinence
  • Renewed responding
  • 3 stimuli
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22
Q

Forced abstinence

A

Extinguishes drug seeking behavior (CR)

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23
Q

Renewed responding

A

Some stimuli are effective in reinstating drug-seeking= reinstatement

24
Q

Stimuli

A
  1. Drug priming (US)- delivering small dose of drug to animal
  2. Stress
  3. CS’s- anything paired with drug uses (environmental cues)
25
Q

Biopsychosocial Model

A

Includes pharmacological, biological, and psychological/ sociocultural factors that influence addiction risk

26
Q

CS’s, stress, or drug exposure […] drug-seeking

A

CS’s, stress, or drug exposure reinstate drug-seeking

  • reinstatement is an animal model of relapse to drug use after abstinence
27
Q

Drug detoxification

A

Elimination of drug form one’s system and passage through the abstinence syndrome

28
Q

Impulsive Stage

A
  • driven by positive reinforcement, drug reward properties
  • reward circuitry- activated
  • generally occurs early in drug using behavior
29
Q

Compulsive Stage

A
  • driven by negative reinforcement; removal of negative stimuli (withdrawal/ abstinence)
  • recruitment of anti-reward circuitry
  • generally occurs later in drug using behavior
30
Q

Stages of substance use

A
  1. Preoccupation with anticipation of obtaining and using substance
  2. Binge use and intoxication from substance
  3. Withdrawal and associated negative effect
31
Q

The […] posited that strong affective responses are followed by their opposite

A

The opponent process model posited that strong affective responses are followed by their opposite

32
Q

Opponent process model

A

Neural mechanisms responsible for affect were organized such that any stimulus that provides initial strong affective reaction automatically sets in motion on opposing affective response that is experienced after initial stimulus ends

33
Q

Opponent process model: nondependent

A

A process: reward

B process: withdrawal

34
Q

Opponent process model: dependent

A

A process: tolerance

B process: anti-reward

35
Q

Reward pathway

A

VTA—> Nuc Acc (VS)—> ventral pallidum

*also medial frontal cortex, amygdala, septal area, and olfactory tubercles

36
Q

Antireward

A

Central nucleus of amygdala—> BNST

Increased NE, increased cotropin- releasing factor, increases dynorphin

*after reaching addiction

37
Q

DA is critical in reward

A
  • Mesolimbic and mesocortical pathways
  • incentive sensitization theory
  • Opioid, GABA, nACh receptors are also important
  • D2 affinity&raquo_space; D1 affinity; D1 receptors are more important for drug reward
38
Q

Mesolimbic and mesocortical pathways

A
  • DA transmission from VTA to N accumbens and PFC

- Essentially all drugs of abuse increase DA signaling in the reward pathway

39
Q

Incentive sensitization theory

A

Drug liking vs wanting

  • certain stimuli become extremely salient and acquire incentive properties

Liking: euphoria, “high”
Wanting: craving
- the incentive salience
- stimuli associated with drug use become attention-getting, desirable

40
Q

Alcohol

A

Increases GABAa and DA in NAcc

41
Q

[…] underlie the transition to addiction

A

Neuroadaptations underlie the transition to addiction

  • Tolerance
  • Recruitment of the antireward system
  • Allostasis of hedonic state
42
Q

Neuroadaptation

A

Pertains to persistent neurobiological changes that can encompass NT activity, gene expression, cellular structure, and neural circuitry

43
Q

Allostasis

A

Physiological, behavioral, or psychological variable that is repeatedly challenged maintained stability by changing its set point

44
Q

Tolerance

A

Decreased activity in the reward circuitry

45
Q

Recruitment of the antireward system

A

Increased release of NE, CRF, and dynorphin

46
Q

Allostasis of hedonic state

A

Change in set points addict uses to feel “normal”

47
Q

Dysfunction in the PFC contributes to the […] phase

A

Dysfunction in the PFC contributes to the preoccupation/ anticipation phase

  • PFC is essential for behavioral control
  • PFC exerts “top-down” control over striatal systems
48
Q

3 main pathways for PFC dysfunction

A
  1. Dorsolateral circuit that projects from dorsolateral PFC (DLPFC) —> dorsolateral caudate nucleus
  2. Ventromedial circuit that connects anterior cingulate cortex with NAcc
  3. Orbitofrontal circuit that projects from orbitofrontal cortex
49
Q

PFC dysfunction in addiction is characterized by

A

Intrusive thoughts; craving (motivation); poor impulse control

50
Q

The transcription factor […] is important in driving molecular changes underlying addiction

A

The transcription factor FosB is important in driving molecular changes underlying addiction

  • Drug administration rapidly induces FosB
  • FosB-induced changes in gene expression
  • epigenetic mechanisms (changes in gene expression increase risk)
51
Q

Drug administration rapidly induces FosB

A

N Acc and dorsal striatum

52
Q

FosB-induced changes in gene expression

A
  • DNA methylation represses transcription (chromatin compaction)
  • Histone acetylation promotes transcription (opens chromatin)
53
Q

Genetic Factors of Addiction

A
  • 0.3-0.8 for heritability of substance use disorders seen in adoption and twin studies
  • Common disease-common variant hypothesis
  • Common disease-rare variant hypothesis
54
Q

Common disease-common variant hypothesis

A

Genetically based susceptibility to neuropsychiatric disorders stems from pool of risk-conferring gene alleles are possessed in common throughout population

55
Q

Common disease-rare variant hypothesis

A

Neuropsychiatric disorders are extremely heterogenous in genetic risk alleles

Neuropharmacology (15 decks)

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