Pharmacology of reward [2] Flashcards
Ventral striatum, aka Nucleus accumbens plays what role in reward?
VTA releases DA into NA = pleasure perceived
- final common pathway of reinforcement and reward is the mesolimbic dopamine pathway
- fxn as the interface betwn th elimbic emotional motivational information and extrapyramidal regulation of motor behavior
amygdala role in brain reward pathways
integrative structure projecting to VTA and NA (releasing Glutatmate) and allows for MEMORY of pairing stimulus with reward
(critical to formation of stimulus-ward associations)
Prefrontal cortex role in brain reward pathways
crtitical for executive fxn:
provides CONTROL over impulses from destructive behavior
- impaired during chronic drug abuse
Drugs of abuse act via multiple NT systems
Share final common pathway (mesolimbic DA pathway)
What do they all increase and where?
Increase DA release in NA
(but other NTs that act on DA neuron:
- 5HT
- Cannabinoid
- ACh
- Enkephalin
Is greater addiction potential associated with more direct or indirect effect on DA release?
Direct effect (more intense)
Natural reinforcers release Glu from where to where?
Amygdala → VTA
(Amygdala neurons release Glu)
gives you emotional cues to achieve action
signal prospect of pleasure-reward from natural reinforcers and provides motivational state to achieve it (learning naturally)
*remember, learning is conditioned in amygdala
Drug of abuse skips this step
(note that Amyg also → to NA)
Drug induces DA release from where to where?
VTA → NA
(VTA neuron releases DA)
*more explosive than natural reinforcers
Fun
potentiation of conditioned award
DA release from where to where induced Drug seeking behavior when presented with Cues?
- what causes it?
VTA → Amygdala
(VTA neuron releases DA)
This is due to repeated drug exposure Pathologic learning (pathologic bursts of DA)
*remember, learning is conditioned in amygdala
Reactive reward system consists of what?
VTA, NA, and Amygdala
this system fxn to signal immediate prospect of either pleasure or pain and provides MOTIVATIONAL and BEHAVIORAL drive to achieve that pleasure to avoid that pain
Drug addiction hijacks normal reward circuitry.
Reflective reward system involves connection from what to what?
Connections from Prefrontal cortex → nucleus accumbens
complementary and competitive component of reactive reward system
- built over time with INFLUENCES (genetics, experience, peer pressure, ect)
*note: with addiction:
(weakening of executive fxn - PFC-NA pathways )
(strengthening of working memory-habit - striatal-cortical pathways)
Conditioning to reward cues
steps
- first time drug is taken → immediate DA release (from VTA to A + NA)
- Corresponding exp → wow!
- Amygdala “learns” that drug-taking is pleasurable
Compulsive Drug use - addiction
steps
- 2 Amygdala learns drug and cues (to VTA) cause pleasure
- Drug cues lead to DA release in NA triggers output to thalamus and cortex
- in absence of activity from reflective ward system drug-seeking initiated
Cocaine:
- molecular target
- mode of action
- effect on DA neurons
- molecular target: Dopamine transporter (DAT)
- mode of action: inhibitor
- effect on DA neurons: blocks DA uptake
DAT INHIBITOR → INCREASE DA LEVELS
Methamphetamine
- molecular target
- mode of action
- effect on DA neurons
- molecular target: Dopamine transporter (DAT)
- mode of action: reverses transporter
- effect on DA neurons: DA releaser
DAT REVERSED → DA RELEASER
Nicotine
- molecular target
- mode of action
- effect on DA neurons
- molecular target: nicotinic receptor
- mode of action: agonist
- effect on DA neurons: Excitation
NICOTINIC RECEPTOR AGONIST → EXCITES DA RELEASE
