pharmacology of reward

Question 1

Normal function of reward pathway

Answer 1

Mediate pleasure perception (reward) and strengthen behaviors (reinforcement) associated with natural reinforcers. Produces motivational states that modulate physiological-behavioral responses ensuring survival and reproduction. Complementary pathway to networks for learning about dangerous stimuli (fear)

Question 2

Structures involved in reward

Answer 2

nucleus accumbens (the major component of the ventral striatum), the amygdala, hippocampus, lateral hypothalamus, and prefrontal cortex, all receiving dopaminergic innervation from cell bodies in midbrain ventral tegmental area.

Question 3

Major components of reward and reinforcement circuitry

Answer 3

Ventral Tegmental Area [VTA] and Nucleus Accumbens [NA] -Function as interface between limbic emotional-motivational information and extrapyramidal regulation of motor behavior

Question 4

Function of hippocampus in reward pathway

Answer 4

•Memory circuit that mediates associations between biologic stimuli (or drugs) and environmental cues

Question 5

Function of amygdala in reward pathway

Answer 5

•Integrative structure that is critical to formation of stimulus-reward associations

Question 6

Which pathway is responsible for weakening of executive function in drug addiction

Answer 6

Prefrontal cortex-ventral striatum pathway

Question 7

How do drugs of abuse activate the reward pathway

Answer 7

same as physiologic activation: ventral tegmental area activation releases dopamine onto nucleus accumbens neurons > perceived pleasure

Question 8

What are natural reinforcers

Answer 8

produce sensory cues that activate reward pathway

Question 9

List steps of reactive reward system

Answer 9

Natural reinforcers activate amygdala to VTA signals >VTA releases dopamine at nucleus accumbens OR drugs of abuse induce dopamine release (more powerful) > repeated drug exposure causes pathologic learning from VTA to amygdala to trigger drug seeking behavior when drug cues are present > amygdala to NA signals trigger emotional memories by drug cues that then initiates behavior to seek drugs

Question 10

Functions of prefrontal cortex in reflective reward system

Answer 10

Orbitofrontal:regulating impulses. Dorsolateral: analysis of situation. Ventromedial: integration with emotions

Question 11

compare reactive and reflective reward systems

Answer 11

reactive: consists of VTA which projects DA neurons to nucleus accumbens and amygdala which connects to both VTA and NA. Involved in drug addiction and short term rewards. Reflective: Prefrontal cortex connects to nucleus accumbens with infleunces from genetics, experiences and can focus final output of reward systm into beneficial long term behavior.

Question 12

Discuss how rate of onset of action affects drug abuse potential

Answer 12

•Abuse liability increased with faster of onset of action

Question 13

Discuss how route of administration affects drug abuse potential

Answer 13

Inhalation: highly addictive, onset within 7 seconds, cocaine, nicotinne, meth, cannabis. IV: highly addictive, onset within 15-30 seconds, intense rush like feelings, most dangerous route (overdose, infecions). Mucus membrane: onset within 3-5 minutes. Oral: onset 20-30 minutes, prevents withdrawal symptoms

Question 14

Discuss how termination of effects affects drug abuse potential

Answer 14

Drugs with shorter half lives have higher abuse potential and more severe withdrawal effects. This leads to continued drug administration to prevent withdrawal

Question 15

compare heroin and methadone

Answer 15

Heroin (short t1/2) more addicting than methadone (long t1/2). Heroine users experience withdrawals, methadone does not