Pharmacology of reward Flashcards

1
Q

brain structures in brain reared pathway

A

1) VTA = dopamine releasing neurons at midline on floor of midbrain
2) VTA and nucleus accumbens = reward and reinforcement (interface limbic emotional-motivation and EP regal of motor)
3) amygdala = formation of stimulus-reward assoc
4) hippocampus = memory circuit for assoc btwn biologic stim (or drug) and environment
5) prefrontal cortex = exec function for control over impulses from destruction

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2
Q

structures inside nucleus accumbens, amygdala, hippocampus, lateral hypothal, prefrontal cortex all receive DA from where?

A

cell bodies in midbrain VTA

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3
Q

normal function of reward path

A

mediate pleasure perception (reward and strengthen behaviors assoc with natural reinforcers

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4
Q

reactive reward system consists of (3)

A

1) VTA = DA neuron cell bodies that respond to glut
2) nucleus accumbens = contains medium spiny neurons release GABA; site of DA neuron projection
3) amygdala = connection to both VTA and NA; house neurons release glut

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5
Q

function of reactive reward

A

signal immediate prospect of either pain (negative) or pleasure (positive) and provides motiv to achieve pleasure or avoid pain

ex= food, water, sex to activ reward

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6
Q

final common path of reinforcement and reward

pleasure NT?

A

mesolimbic dopamine pathway = VTA to nucleus accumbens = pleasure center

pleasure NT = dopamine

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7
Q

VTA activation releases ___ where

A

release DA on to nucleus accumbens neurons

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8
Q

define reinforcing stim

A

incr probability that behaviors paired will be more repeated

more intense and more direct effect on DA release, more addictive

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9
Q

dopaminergic neurons do not
signal ___

but they do signal ___

A

do not signal reward but signal even that warrants attention (learning)

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10
Q

what happens in repeated drug exposure

A

1) addictive drug = incr DA release more than natural
2) strong but inappropriate signal
3) plasticity in glut –> LTP –> strengthens connection btwn 2 neurons

quick and constant

4) also DA neurons in VTA respond to glut and recruited earliest during repeated drug exposure

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11
Q

repeated drug exposure results in ___ learning (pathway) to trigger drug seeking behavior with drug cues

A

pathologic learning

VTA –> amygdala

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12
Q

what happens after learning conditioned in amygdala

A

connection back to VTA = detector for anything relevant to prior drug experience

amygdala to nucleus accumbens –> signal emotion memories from internal/ext cues to initiate impulsive-automatic-obligatory actions to find drugs

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13
Q

Net result to drug addiction

A

reactive reward hijacks normal circuitry

tolerance develops to release of DA by normal biological stim

also, every use of drug = large release of DA to promote NEW LEARNING (new assoc btwn drug and environ or reinforce inapprop learning about drug cues with INCR GLUT)

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14
Q

dopamine hypothesis of addiction

A

drugs of abuse activate dopamine in mesolimbic system

more dopamine released or available at nucleus accumbens, more addictive

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15
Q

mechanisms of how DA levels can incr

A

1) GABAergic inhib (VTA)
2) reuptake inhib
3) ACh receptors

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16
Q

mechanisms of how DA levels can incr

GABAergic inhib

A

1) abuse drug hyperpol GABAergic neuron –> disinhibit DA neuron –> fire more –> release more DA
2) effects = decr anxiety, behavioral disinhib, sedation, euphoria

17
Q

examples of GABAergic inhib

A

1) barbiturates
2) benzo
3) etoh
4) opiates

18
Q

mechanisms of how DA levels can incr

reuptake inhib

A

allows DA and other monoamines to hang out longer in clef

19
Q

mechanisms of how DA levels can incr

examples of reuptake inhib

A

cocaine

amphetamines (directly incr DA release)

20
Q

mechanisms of how DA levels can incr

ACh receptors

A

mimic ACh at presynap nicotinic receptor site = excite DA neurons to release DA in nucleus accumbens

21
Q

mechanisms of how DA levels can incr

ex of ACh receptor

A

Nicotine

22
Q

drugs with abuse potential induce DA release to nucleus accumbens (more or less) than natural

A

more

23
Q

drugs with abuse potential

rate of onset of action

A

incr abuse with faster onset

For cns, inhalation > IV > muc membrane > oral

24
Q

drugs with abuse potential

inhalation route
benefits
ex drugs

A

can titrate blood levels pricely

cocaine, nicotine, meth, cannabis

25
Q

drugs with abuse potential

IV route

A

most intense rush feelings

most dangerous route –> exaggerated rxn, infection, overdose

26
Q

drugs with abuse potential

mucous membrane

A

via insufflation

more rapid and intense than oral b/c bypass liver

27
Q

drugs with abuse potential

oral

A

easiest
can’t get rush
prevents withdrawal so used in treatment

28
Q

drugs with abuse potential
termination

length of half life

A

shorter half life = higher abuse potential

29
Q

drugs with abuse potential

acute considerations

A

quick offset –> freq admin –> incr likelihood for abuse

inhalation of cocaine (free base) > addicting than insufflation (flakes)

30
Q

drugs with abuse potential

chronic considerations

A

withdrawal effect more severe for short half-life

–> keep taking drug to prevent withdrawal

heroin > addicting than methadone