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Neuropharmacology > DA 3 > Flashcards

DA 3 Flashcards

1
Q

Familial histories

A

good for single gene diseases

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2
Q

Genome wide association studies (GWAS)

A

uses larger populations but isn’t hypothesis driven

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3
Q

Copy number variations (CNVs)

A

Examines genomes for deletions or duplications of regions (few kilo-bases to mega-bases)

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4
Q

Familiar histories in schizophrenia

A

Disrupted in schizophrenia 1 (DISC1)
translocation between chromosomes 1 and 11, which has also been implicated in depression, bipolar, autism and other mental disorders ( not found in GWAS)

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5
Q

How does a GWAS work?

A

If one type of the variant (one allele) is more frequent in people with the disease, the SNP is said to be “associated” with the disease
(Initially exons only because of cost, more disease than seeing links to regulation, whole genomes too)

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6
Q

Copy number variations and schizophrenia

A

Deletions, translocations and duplications of regions are sporadic (as 2/3 schizophrenia cases)

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7
Q

which genes have familial studies indicated in schizophrenia?

A 
DISC1 (synapse function)
NRG1 (synapses)
RELN (synapses)
COMT
DRD2
PDE4B
PRODH (Glu synthesis)
AKT-1 (IC signalling)
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8
Q

which genes have GWAS indicated in schizophrenia?

A 
NRG1
RELN
ZNF804A
HIST genes
Notch4
VMAT2
CACNA1C
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9
Q

which genes have CNV studies indicated in schizophrenia

A

GLUR7
ERB4 (TKR for NRG1)
NRXN1
SLC1A3

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10
Q

Of the genes implicated in schizophrenia which are developmental?

A

NRG1
RELN
Notch4

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11
Q

which features schizophrenia does not yet have a genetic link established?

A

Changes in brain region size

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12
Q

Schizophrenia associated genes (and the pathways, in relation to drug treatments)

A

Diagram

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13
Q

DISC1

A

Expressed in all brain regions at birth but high in:
olfactory bulb, cortex, hippocampus, hypothalamus, cerebellum
In adult: highest in hippocampus
(present in neurons AND glia)
Scaffold Protein linked to neurodevelopment and synaptic function

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14
Q

DISC1 interactions

A

Diagram

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15
Q

DISC1 function in the synapse

A 
Spine number 
Spine size
AMPA receptor expression 
Frequency of spontaneous
release
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16
Q

DISC1 in the synapse

17
Q

In relation to reward, what does dopamine signal?

A

Dopamine is now thought of as a reward prediction signal

18
Q

which natural activities are a pleasure pathways involved?

A

Food, water, sexual activity (expand)

19
Q

Reward inducing drugs

A

Ethanol; opiates (reduce inhibition to dopamine neurons); cocaine (monoamine reuptake inhibitor); amphetamine (stimulates monoamine release); nicotine and cannabinoids (increase dopamine release)

20
Q

Mesolimbic system

A

emotion, memory, thoughts and perception

conserved throughout the animal kingdom

21
Q

Reward pathways

A

diagram(s)

22
Q

What happens when something is as expected?

A

expected = tonic (D2R)

23
Q

What happens when something is better-than-expected?

A

better than expected = phasic (D1R)

24
Q

What happens when something is worse than expected?

A

pause in activity

25
Q

What might explain why roots of drug administration that achieve fast/high DA concentrations are more rewarding?

A

high DA release cause D2R → D1R stimulation = reward

26
Q

Which methods of drug administration almost addictive?

A

Fastest methods for high onset of the most addictive

27
Q

Ventral palladium and reward

A

Morgane (1961): lesions of VP lead to aphagia (reduced eating) and adipsia( reduced drinking) in rats
1990’s: lesions of VP reduce ‘liking’ for sucrose -> effect can be mimicked by infusion of GABA agonists (eg muscimol) into VP
Humans with VP partial lesions report decreased ‘cravings’ and ‘pleasure’
from: food, recreational drugs

28
Q

Components of reward

A

Liking, wanting and learning

29
Q

Liking

A

Hedonic impact

30
Q

Wanting

A

Incentive salience

31
Q

Learning

A

Predictive associations and cognitions

32
Q

Experiment: electrodes placed in VP under control of a lever push by rat

A

Result: rat presses the lever more times when the stimulus is applied than. when it is not

33
Q

Experiment: Optogenetic activation of DA-containing neurons

A

Result: monkey prefers choice associated with optogenetic activation

34
Q

Pair bonding

A

Activity in the VP increases during sexual arousal (higher in males!): → sex / pornography can be addictive

35
Q

prairie voles and pair bonding

A

Bonds for life

Males have high levels of vasopressin 1 receptors in VP

36
Q

A link between schizophrenia and reward?

A

Increased DA release may lead to aberrant assignment of ‘salience’ to otherwise innocuous stimuli.
aka – over-reaction (+ ve symptoms)
Heightened dopamine signalling may also elevate ‘noise’ in the reward system which ‘drowns-out’ normal reward.
aka – reward is not perceived (-ve symptoms)

Neuropharmacology (20 decks)

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