Pharmacology of Reward

Question 1

Brain structures involved in the reward pathway

Answer 1

• nucleus accumbens (component of ventral striatum)
• amygdala
• hippocampus
• lateral hypothalamus
• prefrontal cortex
• ventral tegmental area = site of cell bodies of dopaminergic neurons

Question 2

Role of brain dopamine systems in learning physiologically relevant behaviors

Answer 2

• fxn of pathway = mediate pleasure + strengthen behaviors associated w/natural reinforcers (food, water, sex)
• produces motivational states ==> ensuring survival and reproduction
• complementary to systems that mediate learning about dangerous/harmful stimuli

Question 3

Drug-related pathologic learning via dopamine

Answer 3

• drug-induced dopamine release = more explosive/pleasurable than w/natural reinforcers
• repeated exposure to drugs ==> pathologic learning to trigger drug-seeking behaviors
• drug use/drug-related cues ==> dopamine release @ nucleus accumbens
  
  • ==> GABA inhibition ==thalamus==> prefrontal cortex ==> inhibition of reflective reward system
  • w/out reflective system ==> drug-seeking behavior

Question 4

Reactive vs. reflective reward system

Answer 4

• reactive
  
  • VTA projects to/releases dopamine @ amygdala and nucleus accumbens
  • fxns to signal immediate (short-term) prospect of pleasure or pain
  • ==> motivational/behavioral drive needed to achieve pleasure/avoid pain
• reflective
  
  • prefrontal cortex ==> nucleus accumbens
  • orbitofrontal = regulats impulses
  • ventromedial prefrontal = integration of impulsiveness and cognitive flexibility via regulation of emotions
  • ==> regulation of behavior to achieve beneficial long-term goals

Question 5

Dopamine hypothesis of addictive drugs (+ examples)

Answer 5

• all drugs w/abuse potential share the property of enhancing dopamine activity in the nucleus accumbens
• Cocaine = blocks DA uptake ==> relative risk of addiction = 5/5
• Methamphetamine = DA releaser ==> RRA = 5
• Nicotine = excitation of DA neurons ==> RRA = 4
• Opiods = disinhibition of DA neurons ==> RRA = 4
• Alcohol/Benzodiazepines = excitation/disinhibition of DA neurons ==> RRA = 3
• Marijuana = disinhibition of DA neurons ==> RRA = 2

Question 6

Impact of rate of onset on abuse liability

Answer 6

• abuse liability of a drug is increased with an increase in the rapidity of the onset of effect

Question 7

Routes of administration impact on abuse liability

Answer 7

• route = related to rapidity of onset
• from most rapid to slowest CNS action:
  
  • inhalation**
    
    • very fast (~7 secs)
    • user is able to better titrate blood levels vs. other methods
  • IV**
    
    • very fast (15-30 secs)
    • ==> intense rush/flash euphoria
  • Mucous membrane absorption
    
    • fast (3-5 mins)
    • faster and more intense (due to bypass of liver) than oral
  • Oral
    
    • slower (20-30 minutes)
    • easy
• **IV and inhalation = most rapid rise in brain levels ==> greatest addiction potential

Question 8

Impact of half-life on abuse liability

Answer 8

• drugs with shortest half-lives = higher abuse potential
• acutely = quick offset ==> frequent administration ==> higher likelihood of loss of control
• chronically = withdrawal effects of short half-life drugs are more intense ==> continued administration to avoid w/drawal sx