Pharmacology of Reward

Question 1

Structures underlying perception of reward/positive reinforcement

Answer 1

• Nucleus accumbens (part of ventral striatum)
• amygdala
• hippocampus
• lateral hypothalamus
• prefrontal cortex
• all of those receive info from cell bodies in ventral tegmental area

Question 2

Ventral Tegmental Area (VTA) and nucleus accumbens

Answer 2

Function in reward and reinforcement as part of a neural circuit that interfaces between limbic emotional-motivational information and extrapyramidal regulation of motor behavior.

Question 3

amygdala

Answer 3

projects b/t VTA and nucleus accumbens

-imp to formation of stimulus-reward associations

Question 4

hippocampus

Answer 4

memory circuit, mediating assoc b/t biologic stimuli and environmental cues

Question 5

prefrontal cortex

Answer 5

critical for executive function

-control over impulses from destructive behavior

Question 6

What is the final common pathway of reinforcement and reward?

Answer 6

-mesolimbic dopamine pathway
=VTA to nucleus accumbens

• sensory cues from natural reinforcers (food, water, etc) activate the reward pathways.
• Stim of VTA by natural reinforcers results in DA release in nucleus accumbens (drugs of abuse also stim DA release in nucleus accumbens)

Question 7

Reactive reward system

Answer 7

• consists of VTA (dopamine cells bodies), nucleus accumbens and the amygdala (connects the two)
• system signals immediate prospect of pleasure or pain and provides motivational and behavioral drive to achieve pleasure/avoid pain
• drug induced DA increase->learning to trigger drug seeking behavior when presented with internal or external cues
• learning conditioned in amygdala, connections back to VTA act as detector for anything relevant to previous drug abuse experience
• amygdala to nuc accumbens signal that emotional memories have been triggered by internal or ext cues and initiate actions (obligatory) to take more drugs
• drug addiction produces changes where reactive reward system hijacks normal reward circuitry.

Question 8

Reflective reward system

Answer 8

• connections from prefrontal cortex to nucleus accumbens:
• orbitofrontal projections may be involved in regulating impulses
• dorsolateral prefrontal projections (DLPFC) in analysis of situation
• Ventromedial prefrontal (VMPFC) may be involved in integration of impulsiveness and cognitive flexibility with its regulation of emotions
• System built over time, influences from: genetics, neurodevel, experience, peer pressure, learning social rules

Question 9

Variables influencing likelihood of drug abuse

Answer 9

-reinforcing properties (feelings of pleasure or relief of negative effect)
(drugs w/ signif dependence liability share property of enhancing DA activity in the nucleus accumbens)
-rapid onset of action: (fastest to slowest: inhalation>IV>mucous membrane absorption (insufflation–snort)>oral)
-shorter half lives have higher abuse liabilities(and withdrawal effects are more severe)

Question 10

drug induced DA release

Answer 10

VTA to NA

• more explosive/pleasurable than w/ natural reinforces
• repeated drug exposures result in pathologic learning (VTA to amygdala) to trigger drug seeking behavior when presented w/ drug cues

Question 11

Amygdala to NA

Answer 11

signals triggering of emotional memories by drug cues that initiates behavior to seek and take drugs
-drug addiction hijacks normal reward circuitry

Question 12

Highest relative risk of addiction

Answer 12

Stimulants (cocaine, meth)

• molecular target: DAT
• impact DA available (cocaine blocks uptake, meth releases DA)

Nicotine (agonist of nicotinic receptor)

Question 13

Which is the most dangerous route?

Answer 13

IV

• rush like feelings
• exaggerated rxns, infections, overdose toxicities

Question 14

Which route will prevent withdrawal sx?

Answer 14

oral

• hard to get rush feelings
• 20-30 mins
• but useful in treatment programs