05 Reward System & Substance Abuse

Question 1

key processes implicated in addictive behavior - psychological level

Answer 1

• drug consumption becomes a habit and is promoted by increased effects of drug cues, stress and priming
• impaired goal-directed control of behavior interferes with the ability to reduce drug intake or remain abstinent in spite of aversive consequences
• negative affect and reduced sensitivity to alternative rewards contribute to the failure of non-drug related rewards to motivate behavioral change

Question 2

key processes implicated in addictive behavior - neural level

Answer 2

• chronic drug intake is associated with increased dopamine release and reorganization of ventral-to-dorsal striatal loops -> impairment of behavioral flexibility and promotion of habitual drug intake, sensitization towards drug cues
• impaired cognitive control is attributed to heritable and environmental factors interacting with neurotoxic and -adaptive changes in PFC and related brain regions
• neuroadaptive processes within limbic and stress hormone systems contributing to negative affect

Question 3

Alcohol use disorder - DSM-5 criteria

Answer 3

• tolerance
• withdrawal
• more use than intended
• unsuccessful efforts to cut down
• spending a lot of time getting, using, or recovering from use
• cravings and urges to use the substance
• uses despite negative physical, psychological or social effects
• not managing to do what you should at work, home or school, because of substance use
• social, occupational or recreational activities given up because of use

Question 4

stages of substance use

Answer 4

• social use
• riskful drinking (women: >20g/day, men: >40g/day)
• mild (2-3 criteria)
• moderate (4-5 criteria)
• severe (6 or more criteria)
• withdrawal

Question 5

symptoms of withdrawal

Answer 5

• autonomic hyperactivity
• increased hand tremor
• insomnia
• nausea or vomiting
• transient hallucinations
• psychomotor agitation
• anxiety
• grand mal seizures

Question 6

genetics of alcoholism

Answer 6

• major influence on the development of alcohol dependence
• any drinker has 5-10% risk of developing alcohol dependence
• 20-50% risk if both parents are alcohol dependent
• 28% risk for fraternal twins
• 54% risk for identical twins
• specific mechanism not understood, polygenic, D2DR mutation with reduced receptor density
• no evidence for typical pre-alcoholic personality

Question 7

alcoholism - epidemiology (Germany)

Answer 7

• riskful drinking: 11% women, 22% men
• alcohol abuse: 3.2 mio. (4%)
• alcohol dependence: 2%

Question 8

substance use disorder - treatment strategies

Answer 8

• detoxification and long-term treatment
• motivational stages of change: precontemplation, contemplation, preparation, action, maintenance, relapse
• connect problems to drinking, don’t confront or argue
• self-help groups
• medications for alcohol detoxification: Clomethiazol, benzodiazepines
• medication for long-term treatment…

Question 9

human reward system

Answer 9

mesolimbic dopamine system
- ventral tegmental area
- nucleus accumbens (ventral striatum)
- responsible for craving, motivational aspect

Question 10

dopamine system and addiction

Answer 10

high, brief bursts of dopamine are required for addiction (but not sufficient)
- directly or indirectly, all addictive drugs trigger exaggerated, transient increases in extracellular DA in Nac
- stimulants and nicotine directly increase DA release at Nac
- opiods, alcohol and phencyclidine (PCP) suppress inhibitory neurons that modulate VTA and Nac
DA surges resemble (and often greatly surpass) physiological increases triggered by natural reinforcers

Question 11

neurotransmitter system and positive reinforcement

Answer 11

positive reinforcement mediated by
- dopamine release (craving, motivation)
- GABA-A receptor activation (calming/relaxing effect)
- inhibition of glutamate NMDA receptor (during withdrawal, facilitation of glutamate system, increased excitability)
- opioid peptide release (pleasure/hedonic aspect of consumption)
- interaction with serotonin system (responsible for secondary depression)

Question 12

evidence for persistent changes in the brain

Answer 12

• tolerance
• withdrawal
• depression and anhedonia when not using
• persistence of craving over years
• lower response to natural rewards
• capacity to relapse even many years of abstinence

Question 13

neural correlates of persistent changes/chronic alcohol consumption

Answer 13

• downregulation of dopamine receptors and dopamine production (lower response to natural rewards)
• downregulation of inhibitory neuronal GABA receptors
• upregulation of excitatory glutamate NMDA receptors
• increased central norepinephrine activity
  -> withdrawal symptoms

Question 14

opiate and alcohol craving

Answer 14

• Naltrexon, a mu-opiate receptor antagonist, reduces relapse risk among some individuals with AUD
• increased mu-opiate receptor availability in ventral striatum / Nac in detoxified individuals -> stronger craving
• cause or consequence of excessive alcohol intake

Question 15

dual system model of addiction

Answer 15

• psychotherapy targeting reflexive system (cognitive control) achieves only moderate and transient effects
• impulsive system must be targeted
• alcohol approach bias is related to activation in Nac and medial PFC
• correlation between amygdala activation and craving
• bias modification training (alcohol needs to be pushed away in 90% of trials) leads to reduced approach bias and reduced cue-reactivity in amygdala

Question 16

Frankfurt’s free will

Answer 16

• first-order desire: “I crave alcohol”
• second-order volition: “I want a certain first-order desire to be my will”
• free will: person is free to choose which first-order desire to be their will, satisfaction of volitions of second order
• Wanton: no second-order volition present
• unwilling addict: second-order volition is present, however, the person is not able to make the abstinence desire their will
• willing addict: second-order volition wants the craving desire to be the will