L6 - neurotransmitter receptor signalling

Question 1

how does alcohol impact neural function

x4

Answer 1

acts as a neurotransmitter receptor
destabilises lipid polar heads - disrupts bilayer
interacts with channel proteins
stimulates Gas signalling

Question 2

how does acute alcohol modulate glutamatergic neurotransmission
x2

Answer 2

acts as a non-competitive antagonist - -ve allosteric modulator
reduces glutamate release from pre-synaptic terminal

Question 3

effect of acute alcohol on glutamatgeric signalling

Answer 3

INHIBITION

Question 4

how does alcohol reduce Glu release from pre-synaptic terminal

Answer 4

increases activity of mGlu2/3
metabotropic receptor
causes Gi/o signalling (inhibitory)

Question 5

what is required to activate an NMDA receptor

Answer 5

glutamate
co-agonist at modulatory site
e.g. glycine, D-serine

Question 6

Mg2+ block

Answer 6

NMDA receptor
voltage-sensitive
present at physiological concentrations of Mg2+
disappears after depolarisation

Question 7

what causes depolarisation of NMDA receptors

Answer 7

cation channel opening

Ca2+ and Na+ influx

Question 8

why are different brain regions impacted differently by alcohol

Answer 8

different glutamate receptors have different alcohol sensitivity

Question 9

overall effect of chronic alcohol on glutamatergic signalling

Answer 9

causes compensatory adaptions to increase Glu release and transmission

Question 10

what are the compensatory Glu adaptations to chornic alcohol use
x4

Answer 10

1. increased NMDA/AMPA R on post-synaptic membrane
2. increased ion channel conductance
3. decreased glial uptake of neurotransmitter
4. desensitisation of pre-synaptic mGlu R -

Question 11

effect of desensitisation of mGlu R on pre-synaptic membrane

Answer 11

reduced response to Glu
less Gi/o signalling
more Glu released into synaptic cleft

Question 12

glutamate-mediated acute alcohol behavioural effects

Answer 12

reduced signalling

- amnesia, memory loss

Question 13

glutamate-mediated chronic alcohol behavioural effects

Answer 13

increased signalling

• seizures, brain damage
• anxiety

Question 14

foetal alcohol syndrome

Answer 14

glutamatergic signalling impaired in foetus

therefore offspring has fewer NMDA receptors

Question 15

effect of acute alcohol on GABAergic signalling

Answer 15

acts as a +ve allosteric modulator
increased Cl- influx
enhanced GABA release

Question 16

effect of sedative drugs on GABA receptors

Answer 16

act as positive allosteric modulators

enhance GABA R activity via modulatory site

Question 17

activated GABAa receptor

Answer 17

anion channel opening
Cl- influx
hyperpolarisation

Question 18

effect of acute alcohol on neurosteroid release

Answer 18

increases neurosteroid release
causes positive allosteric modulation of GABAa receptors
enhanced GABA signalling

Question 19

effect of chronic alcohol on GABAergic transmission

Answer 19

reduced impact

changes GABAa receptor subunit composition

Question 20

impact of alcohol changing GABAa receptor subunit composition

Answer 20

reduces sensitivity to alcohol

change in localisation

Question 21

what causes withdrawal after chronic exposure

Answer 21

rapid reversion of GABA subunit changes

Question 22

GABA-mediated effects of acute alcohol on behaviour

Answer 22

enhanced signalling
sedative
anxiety-reduced
impaired coordination

Question 23

GABA-mediated effects of chronic alcohol on behavioru

Answer 23

reduced signalling
alcohol tolerance
seizures
hyper-excitatbiltiy
tremour

Question 24

effects of acute alcohol on opioid synthesis and release

Answer 24

cause increase synthesis and release
eg endorphins
neuromodulators reinforce effects of alcohol

Question 25

opioid-mediated effects of acute alcohol on behaviour

Answer 25

increased synthesis and release euphoria excitement reinforces other effects

Question 26

opioid-mediated effects of chronic alcohol on behaviour

Answer 26

reduced opioid signalling | dysphoria

Question 27

how does alcohol effect glial function

Answer 27

effects astrocyte expression | effects excitatory amino acid transporters

Question 28

how do glial cells modulate synaptic transmission

Answer 28

release gliotransmitters and neurotransmitters

Question 29

is full sepctrum of alcohol's pharmalogical action clear?

Answer 29

no | unclear

Question 30

why is there tremendous diversity in GABA receptor subunits

Answer 30

they are hetergenous

Question 31

2 categories of alcohol effects on neural function

Answer 31

specific | non-specific

Question 32

3 specific effects of alcohol on neural function

Answer 32

interacts directly with channel proteins stimulates G alpha s signalling acts at the neurotransmitter binding site

Question 33

where do the specific effects of alcohol act

Answer 33

receptor site

Question 34

where do the non-specific effects of alcohol act

Answer 34

plasma membrane

Question 35

what are the non-specific effects of alcohol on neural function

Answer 35

interaction with polar heads of phospholipids alteration of lipid composition disturbance of relationship of proteins in the membrane

Question 36

define reinforcement

Answer 36

Strengthening probability of future behaviour.

Question 37

what causes reinforcement of alcohol

Answer 37

enhanced opioid synthesis and release in acute alcohol consumption

Question 38

what mediates reinforcement

Answer 38

the mesolimbic dopamine pathway “reward” system | VTA to limbic system

Question 39

effect of withdrawal on GABAa receptors

Answer 39

rapid reversal of receptor subunit changes | causes withdrawal symptoms

Question 40

tonic inhibition

Answer 40

long-lasting | makes it more difficult to fire action potentials

Question 41

birds eye view of GABAa receptor subunits

Answer 41

``` a1 (GABA binding site) B2 a2 (GABA binding site) B2 y2 (Benzodiazepine binding site) ```

Question 42

benzodiazepine

Answer 42

anxiety-reducing, sedative drug acts via enhancing GABA signalling +ve allosteric modulator of GABAa

Question 43

how many GABA receptor subunits

Answer 43

5 | pentamer

Question 44

effects of different blood alcohol concentrations

Answer 44

0. 05% - relief from anxiety, social boost 0. 08% - impaired cognition and motor function 0. 40% - death in 50% of people

Question 45

effect of increased alcohol consumption on hippocampal size

Answer 45

decreases size of hippocampus

Question 46

which receptor effects memory

Answer 46

NMDA | LTP required for memory