Pharmacology of reward [2] Flashcards Preview

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Flashcards in Pharmacology of reward [2] Deck (21):
1

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

2

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)

3

Prefrontal cortex role in brain reward pathways

crtitical for executive fxn:
provides CONTROL over impulses from destructive behavior
- impaired during chronic drug abuse

4

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

5

Is greater addiction potential associated with more direct or indirect effect on DA release?

Direct effect (more intense)

6

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)

7

Drug induces DA release from where to where?

VTA → NA
(VTA neuron releases DA)
*more explosive than natural reinforcers

Fun
potentiation of conditioned award

8

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

9

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.

10

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)

11

Conditioning to reward cues
(steps)

1. first time drug is taken → immediate DA release (from VTA to A + NA)
2. Corresponding exp → wow!
3. Amygdala "learns" that drug-taking is pleasurable

12

Compulsive Drug use - addiction
(steps)

1.2 Amygdala learns drug and cues (to VTA) cause pleasure
3. Drug cues lead to DA release in NA triggers output to thalamus and cortex
4. in absence of activity from reflective ward system drug-seeking initiated

13

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

14

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

15

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

16

Opioids
- molecular target
- mode of action
- effect on DA neurons

- molecular target: µ opioid receptor (Gi/o)
- mode of action: Agonist
- effect on DA neurons: Disinhibition

µ OPIOID RECEPTOR AGONIST → RUSH FEELINGS

17

Fastest pharmacokinetics route 4 drugs of abuse?

Inhalation
- onset w/in 7 seconds
- highly addictive

straight shot to the brain

(cocaine, nicotine, meth, cannabis)

18

What is the most dangerous route of drug abuse?

IV
Rush feeling

19

Most useful route of administration in tx programs

Oral
- prevent w/drawl symptoms
- difficult to obtain rush feelings
- delayed onset: 20-30 min

20

longer or shorter half lives have higher abuse potential??

shorter

(quick offset → leads to frequent administration)
Withdrawal effects more severe


(note: long acting: slow to get high, slow to get off)

21

Withdrawl from what is dangerous, opioids (heroine) or OH, BDZ, barbiturates

OH, BDZ, barbiturates

- 5-10% seizures
goes from CNS depression to excitation