Pharmacology of reward

Question 1

Identify the brain structures and systems that are thought to comprise the brain reward pathway.

Answer 1

VTA–>Nucleus accumbens-
Major components of reward and reinforcement circuitry
Function as interface between limbic emotional-motivational information and extrapyramidal regulation of motor behavior

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

prefrontal cortex-Critical for executive function in providing control over impulses from destructive behavior - impairment important mediator of loss of control

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

Question 2

Describe the central role of brain dopamine systems in learning physiologically relevant behaviors and possible contributions of other neurotransmitter systems.

Answer 2

VTA activation releases DA onto NA neurons–> pleasure perceived and identifies stimulating activity as one to be repeated

Question 3

Describe the interaction of drugs of abuse with brain reward pathways in the development of addictive behaviors.

Answer 3

Progressive behavioral syndrome->compulsive drug-seeking and drug-taking despite serious consequences
Loss of ability to make choices promoting happiness and survival
Weakening of executive function ->PFC-NA pathways
Realization of destructive nature of addiction - unable to alter behavior
Strengthening of working memory-habit ->striatal-cortical pathways
Pathologic effects of drugs mediated in large part via actions – acute and chronic – on the brain Reward Pathway

Question 4

Conditioning to reward cues

Answer 4

[1] First time drug taken causes immediate release of dopamine

[2] Corresponding experience of pleasure  wow!

[3] Amygdala “learns” that drug-taking is a pleasurable experience
[1,2] Amygdala learns drug and cues cause pleasure – may signal relief from craving

[3] Drug cues lead to DA release in NA  triggers output to thalamus and cortex [4]

[4] In absence of activity from reflective reward system  drug-seeking initiated

Question 5

Amygdala to VTA

Answer 5

Amygdala to VTA functions to signal prospect of pleasure-reward (relevance detection) from natural reinforcers and provides motivational state to achieve it

Question 6

VTA–>NA

Answer 6

Drug-induced DA release (VTA to NA) is more explosive (pleasurable) than with natural reinforcers

Question 7

VTA–> amygdala

Answer 7

Repeated drug exposures result in pathologic learning (VTA to amygdala) to trigger drug-seeking behavior when presented with drug cues

Question 8

Amygdala to NA

Answer 8

Amygdala to NA signals triggering of emotional memories by drug cues that then initiates behavior to seek and take drugs

Question 9

cocaine

Answer 9

stimulant stops dopamine reuptake by blocking by inhibiting DAT

Question 10

methamphetamine

Answer 10

DAT, reverses transporter, dopamine releaser

Question 11

Nicotine

Answer 11

nicotinic receptor, agonist, excitation of DA neurons

Question 12

Opioids

Answer 12

agonist u opioid receptor G i/o, disinhibition of dopamine neurons

Question 13

are withdrawal effects more severe with long or short half lives?

Answer 13

short

Question 14

do drugs with short or long half lives have higher abuse potential

Answer 14

short

Question 15

how is route of administration correlated with abuse liability?

Answer 15

quicker in, bigger high quicker out. Abuse liability increased with faster of onset of action