L6 - neurotransmitter receptor signalling Flashcards
how does alcohol impact neural function
x4
acts as a neurotransmitter receptor
destabilises lipid polar heads - disrupts bilayer
interacts with channel proteins
stimulates Gas signalling
how does acute alcohol modulate glutamatergic neurotransmission
x2
acts as a non-competitive antagonist - -ve allosteric modulator
reduces glutamate release from pre-synaptic terminal
effect of acute alcohol on glutamatgeric signalling
INHIBITION
how does alcohol reduce Glu release from pre-synaptic terminal
increases activity of mGlu2/3
metabotropic receptor
causes Gi/o signalling (inhibitory)
what is required to activate an NMDA receptor
glutamate
co-agonist at modulatory site
e.g. glycine, D-serine
Mg2+ block
NMDA receptor
voltage-sensitive
present at physiological concentrations of Mg2+
disappears after depolarisation
what causes depolarisation of NMDA receptors
cation channel opening
Ca2+ and Na+ influx
why are different brain regions impacted differently by alcohol
different glutamate receptors have different alcohol sensitivity
overall effect of chronic alcohol on glutamatergic signalling
causes compensatory adaptions to increase Glu release and transmission
what are the compensatory Glu adaptations to chornic alcohol use
x4
- increased NMDA/AMPA R on post-synaptic membrane
- increased ion channel conductance
- decreased glial uptake of neurotransmitter
- desensitisation of pre-synaptic mGlu R -
effect of desensitisation of mGlu R on pre-synaptic membrane
reduced response to Glu
less Gi/o signalling
more Glu released into synaptic cleft
glutamate-mediated acute alcohol behavioural effects
reduced signalling
- amnesia, memory loss
glutamate-mediated chronic alcohol behavioural effects
increased signalling
- seizures, brain damage
- anxiety
foetal alcohol syndrome
glutamatergic signalling impaired in foetus
therefore offspring has fewer NMDA receptors
effect of acute alcohol on GABAergic signalling
acts as a +ve allosteric modulator
increased Cl- influx
enhanced GABA release
effect of sedative drugs on GABA receptors
act as positive allosteric modulators
enhance GABA R activity via modulatory site
activated GABAa receptor
anion channel opening
Cl- influx
hyperpolarisation
effect of acute alcohol on neurosteroid release
increases neurosteroid release
causes positive allosteric modulation of GABAa receptors
enhanced GABA signalling
effect of chronic alcohol on GABAergic transmission
reduced impact
changes GABAa receptor subunit composition
impact of alcohol changing GABAa receptor subunit composition
reduces sensitivity to alcohol
change in localisation
what causes withdrawal after chronic exposure
rapid reversion of GABA subunit changes
GABA-mediated effects of acute alcohol on behaviour
enhanced signalling
sedative
anxiety-reduced
impaired coordination
GABA-mediated effects of chronic alcohol on behavioru
reduced signalling alcohol tolerance seizures hyper-excitatbiltiy tremour
effects of acute alcohol on opioid synthesis and release
cause increase synthesis and release
eg endorphins
neuromodulators reinforce effects of alcohol
opioid-mediated effects of acute alcohol on behaviour
increased synthesis and release
euphoria
excitement
reinforces other effects
opioid-mediated effects of chronic alcohol on behaviour
reduced opioid signalling
dysphoria
how does alcohol effect glial function
effects astrocyte expression
effects excitatory amino acid transporters
how do glial cells modulate synaptic transmission
release gliotransmitters and neurotransmitters
is full sepctrum of alcohol’s pharmalogical action clear?
no
unclear
why is there tremendous diversity in GABA receptor subunits
they are hetergenous
2 categories of alcohol effects on neural function
specific
non-specific
3 specific effects of alcohol on neural function
interacts directly with channel proteins
stimulates G alpha s signalling
acts at the neurotransmitter binding site
where do the specific effects of alcohol act
receptor site
where do the non-specific effects of alcohol act
plasma membrane
what are the non-specific effects of alcohol on neural function
interaction with polar heads of phospholipids
alteration of lipid composition
disturbance of relationship of proteins in the membrane
define reinforcement
Strengthening probability of future behaviour.
what causes reinforcement of alcohol
enhanced opioid synthesis and release in acute alcohol consumption
what mediates reinforcement
the mesolimbic dopamine pathway “reward” system
VTA to limbic system
effect of withdrawal on GABAa receptors
rapid reversal of receptor subunit changes
causes withdrawal symptoms
tonic inhibition
long-lasting
makes it more difficult to fire action potentials
birds eye view of GABAa receptor subunits
a1 (GABA binding site) B2 a2 (GABA binding site) B2 y2 (Benzodiazepine binding site)
benzodiazepine
anxiety-reducing, sedative drug
acts via enhancing GABA signalling
+ve allosteric modulator of GABAa
how many GABA receptor subunits
5
pentamer
effects of different blood alcohol concentrations
- 05% - relief from anxiety, social boost
- 08% - impaired cognition and motor function
- 40% - death in 50% of people
effect of increased alcohol consumption on hippocampal size
decreases size of hippocampus
which receptor effects memory
NMDA
LTP required for memory
