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Pmcol 305 > Neurotransmitters and receptors > Flashcards

Neurotransmitters and receptors Flashcards

1
Q

Dopamine

A

catecholamine
primary driver of reward circuit
VTA → NAC (second phase)

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2
Q

Glutamate

A

amino acid
major role in cue-triggered relapse
LTP/LTD plasticity

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3
Q

GABA

A

major inhibitory neurotransmitter
central to disinhibitory mechanisms of reward

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4
Q

Norepinephrine

A

catecholamine
major source of NE projections in the brain from the locus coeruleus
big role in stress-induced relapse

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5
Q

Acetylcholine

A

receptors on VTA dopaminergic neurons
central to learning and memory in hippocampus and PFC circuits in neocortex and striatum

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6
Q

Serotonin

A

5-HT
monoamine indole
major source is the raphe nuclei
link between low 5HT and impulsivity + violence in addicts

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7
Q

catecholamine

A

neurons with similar structures
dopamine, adrenaline, noradrenaline

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8
Q

monoamine indole

A

monoamines are a class of neurons with similar structure - dopamine, NE, 5-HT
serotonin has an indole ring; slightly varied structure

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9
Q

hedonic tone

A

tonic dopamine release
baseline level of dopamine being released

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10
Q

microdialysis

A

thin electrode placed on brain tissue
measure neurotransmitter levels in specific nuclei directly - single synapse

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11
Q

self-administration

A

controlling own administration of drug
used in experiments of animal behaviour and addiction
via instrumental behaviour

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12
Q

conditioned place preference

A

pairing an environment with stimulation of VTA dopaminergic projections → immediate place preference that persists for several days
time spent in paired environment = representative of drug-seeking behaviour

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13
Q

extinction

A

loss of drug seeking/taking behaviours
produced by antagonists

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14
Q

LTD

A

long term depression
weakening of synaptic transmission between two neurons

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15
Q

LTP

A

long term potentiation
strengthening of synaptic transmission between two neurons downstream of receptors

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16
Q

ionotropic receptors

A

ligand-gated channels through which ions pass in response to a neurotransmitter

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17
Q

metabotropic receptors

A

GPCRs
require G proteins and second messengers to indirectly modulate ionic activity in neurons

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18
Q

specificity

A

sites of LTP are confined to specific contact sites where transmission is occurring

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19
Q

associativity

A

strong stimulation through one pathway will induce LTP for weak pathways at the same site

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20
Q

cooperativity

A

many weak stimuli can induce LTP
threshold effect
constructive interference

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21
Q

persistence

A

potentiation lasts minutes, weeks, months; unique to LTP
dependent on drug, signaling, and adaptations the neurons undergo

22
Q

sympathomimetic

A

response to stimulant drugs mimic the effects of the sympathetic nervous system - increased heart rate, blood pressure, temperature

23
Q

reward circuit

A
  1. descencing glutamatergic pathway to VTA
  2. ascending dopaminergic VTA pathway to NAc
  3. GABA-ergic NAc pathway to ventral pallidum
24
Q

dopamine receptors

A

5 genes (DRD1-5)
GPCRs

25
Q

D1-like type dopamine receptors

A

D1 and D5
coupled to Gs - stimulatory G protein
increases cytoplasmic cAMP via adenylyl cyclase

26
Q

D2-like type dopamine receptors

A

D2, D3, D4
coupled to Gi - inhibitory G protein
decreases cytoplasmic cAMP via adenylyl cyclase

27
Q

measure of addictiveness

A

effort exerted to self-administer is related to degree of reward experienced - reinforcing

28
Q

tonic and phasic dopamine levels

A

tonic level: steady state, hedonic tone
phasic level: erratic, clustering of dopamine release

addictive drugs induce phasic dopamine firing in the NAc

29
Q

vehicle

A

solvent used to dissolve drug
control

30
Q

antagonist

A

interrupt signaling
dopamine antagonists are negative reinforcers that enhance behaviours to reduce administration - shift back to control

31
Q

in vivo synaptic transmission of dopamine release in NAc via microdialysis

A
  1. the first dose results in 200% increase in tonic extracellular level
  2. extracellular dopamine levels fluctuate between 200-300% over baseline
  3. each low point in the fluctuating dopamine level predicts the next self-administered dose - craving
32
Q

tolerance

A

leads to lowered elevation of hedonic tone during chronic use
causes addicts to use higher and higher doses to restore homeostatic dopamine levels

33
Q

withdrawal

A

causes reduction in hedonic dopamine tone = dysphoric state
physical symptoms: cramps, diarrhea, pain

34
Q

sensitization

A

reverse tolerance
enhanced activity

35
Q

pro reward system

A

repeated opioid activity causes decrease in pro reward
at same dose, decreased dopamine release

36
Q

anti reward system

A

repeated opioid activity causes increase in anti reward

37
Q

AMPA receptor

A

ionotropic
form tetramers
undergo chemical modifications to trigger intracellular signaling cascades
major role in long term depression
4 genes (GluA1-4)
fast excitatory transmission

38
Q

NMDA receptors

A

7 genes (1 GluN1, 4 GluN2, 2 GluN3)
ionotropic
co-activated by Glu and Ser/Gly
subunits form heterotetramers - 2 GluN1 and 2 GluN2
critical for synaptic plasticity - LTP/LTD
Ca2+ dependent signaling

39
Q

Glutamate receptors

A

mGlu-R
metabotropic GPCRs (group C)
8 genes (GRM1-8); each gene encodes a receptor - mGluR7A
involved in synaptic plasticity

40
Q

Group I mGlu-R

A

Gq-linked
increase excitotoxicity risk

41
Q

excitotoxicity

A

cell death by too much glutamate - over activation

42
Q

Group II/III mGlu-R

A

Gi/o-linked
decrease excitotoxicity risk

43
Q

mGluR3

A

expressed in nucleus accumbens

44
Q

mGluR7

A

expressed in hippocampus, amygdala, and locus coeruleus

45
Q

NMDAR

A

expressed in hippocampus

46
Q

dopamine prediction error hypothesis of addiction

A

phasic firing of VTA dopaminergic neurons generates a learning signal when an unexpected reward occurs → promotes learning so the reward can be obtained again
once the reward becomes fully predictable, dopaminergic neurons are no longer triggered
neuroplasticity: shift from reward- to goal-seeking

47
Q

NE innervation

A

in locus coeruleus
activates sympathetic responses
major role in stress-induced drug relapse

48
Q

5-HT receptors

A

triggered by hallucinogens and entactogenic drugs
less addictive drugs
bi-synaptic 5-HT inputs to the VTA and NAc from the raphe nuclei

49
Q

acetylcholine activation

A

parasympathetic responses
learning and memory circuits in hippocampus

50
Q

nicotinic ACh receptors

A

display several isoforms with brain region-specific expression including on VTA dopaminergic neurons which underlies addiction to nicotine

51
Q

drugs are pleiotropic

A

cause multiple physiological effects

Pmcol 305 (18 decks)

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