ethanol and the CNS Flashcards
describe the structure of ethanol
small surface area and volume so can therefore squeeze into small spaces in proteins)
describe the properties of ethanol
alipathic
partitions equally well between water and lipid so can cross membranes
contains one hydrogen donor/acceptor so forms weak bonds
can bind to multiple targets to modify their function
acts with low pharmacological potency
why can ethanol reach such high levels?
distributed amongst all body water
why is ethanol different to any other drug in terms of concentration and effects?
very high blood concentrations needed to produce effects on CNS
other drugs would cause serious illness at such levels
how much is 1 unit?
8g (10ml) pure alcohol
what levels of blood alcohol are clinically relevant?
5 - 100 mM
through what 2 general mechanisms does ethanol affect the CNS?
enhancing inhibitory neurotransmission or depressing excitatory transmission (e.g pre/post synaptic mechanism making it more negative so wont fire)
give an example of an inhibitory neurotransmission which is enhanced?
glycine and GABAa receptors
give an example of an excitatory transmission which is depressed?
glutamate receptors
what type of ion channels are GABA, glycine and glutamate and what do they do?
ligand gated
mediate excitatory and inhibitory neurotransmission in the CNS
describe the make up of GABAa receptors
made of 5 subunits
can be a combination of either alpha, beta and gamma or alpha, beta and delta in any amount of each
describe the make up of glutamate receptors
4 subunits
many different types depending on combination of subunits
what is the significance of having many different types of GABA/glutamate receptor?
composition of the receptor can determine its sensitivity to ethanol
where on the receptors could ethanol bind?
extracellular domain
transmembrane domain
what is the major inhibitory neurotransmitter in the CNS and where does it act?
GABA
acts at GABAa receptors
what is the difference between synaptic and extrasynaptic GABA receptors?
extrasynaptic contain delta subunits and are particularly sensitive causing fast, long lasting effects from small amount of ethanol in naïve drinkers
what importance does the makeup of the GABA receptor have?
different components result in different behavioural effects from same alcohol (anxiety, aggression etc)
what do GABA agonists and antagonists do?
agonists mimic effect of alcohol
antagonist reduce effects of ethanol
what is the major excitatory neurotransmitter in the CNS and where does it act?
glutamate
acts at NMDA glutamate receptors
what effect does ethanol do the NMDA receptors and why is this significant?
ethanol inhibits these receptors
therefore anything else that blocks these receptors (NMDA antagonists) has the same effect as alcohol
describe the mesolimbic dopaminergic pathway (reward system of brain)
dopaminergic neurone lies in ventral tegmental area of brain and releases dopamine via medial forebrain bundle to nucleus accumbens area of brain which links to hippocampus etc
how does alcohol cause pleasure and possible cause dependence?
stimulates VTA activating mesolimbic dopaminergic pathway
how can the reward system be activated pharmacologically?
directly or indirectly exciting VTA neurones stimulating release of dopamine which inhibits neurones in NAc
OR
enhancing release of dopamine or preventing its reuptake
OR inhibiting NAc neurones
what changes occur to compensate for CNS depression in prolonged ethanol consumption?
upregulation of NMDA receptors
downregulation of GABA receptors
