ethanol and the CNS

Question 1

describe the structure of ethanol

Answer 1

small surface area and volume so can therefore squeeze into small spaces in proteins)

Question 2

describe the properties of ethanol

Answer 2

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

Question 3

why can ethanol reach such high levels?

Answer 3

distributed amongst all body water

Question 4

why is ethanol different to any other drug in terms of concentration and effects?

Answer 4

very high blood concentrations needed to produce effects on CNS
other drugs would cause serious illness at such levels

Question 5

how much is 1 unit?

Answer 5

8g (10ml) pure alcohol

Question 6

what levels of blood alcohol are clinically relevant?

Answer 6

5 - 100 mM

Question 7

through what 2 general mechanisms does ethanol affect the CNS?

Answer 7

enhancing inhibitory neurotransmission or depressing excitatory transmission (e.g pre/post synaptic mechanism making it more negative so wont fire)

Question 8

give an example of an inhibitory neurotransmission which is enhanced?

Answer 8

glycine and GABAa receptors

Question 9

give an example of an excitatory transmission which is depressed?

Answer 9

glutamate receptors

Question 10

what type of ion channels are GABA, glycine and glutamate and what do they do?

Answer 10

ligand gated

mediate excitatory and inhibitory neurotransmission in the CNS

Question 11

describe the make up of GABAa receptors

Answer 11

made of 5 subunits

can be a combination of either alpha, beta and gamma or alpha, beta and delta in any amount of each

Question 12

describe the make up of glutamate receptors

Answer 12

4 subunits

many different types depending on combination of subunits

Question 13

what is the significance of having many different types of GABA/glutamate receptor?

Answer 13

composition of the receptor can determine its sensitivity to ethanol

Question 14

where on the receptors could ethanol bind?

Answer 14

extracellular domain

transmembrane domain

Question 15

what is the major inhibitory neurotransmitter in the CNS and where does it act?

Answer 15

GABA

acts at GABAa receptors

Question 16

what is the difference between synaptic and extrasynaptic GABA receptors?

Answer 16

extrasynaptic contain delta subunits and are particularly sensitive causing fast, long lasting effects from small amount of ethanol in naïve drinkers

Question 17

what importance does the makeup of the GABA receptor have?

Answer 17

different components result in different behavioural effects from same alcohol (anxiety, aggression etc)

Question 18

what do GABA agonists and antagonists do?

Answer 18

agonists mimic effect of alcohol

antagonist reduce effects of ethanol

Question 19

what is the major excitatory neurotransmitter in the CNS and where does it act?

Answer 19

glutamate

acts at NMDA glutamate receptors

Question 20

what effect does ethanol do the NMDA receptors and why is this significant?

Answer 20

ethanol inhibits these receptors

therefore anything else that blocks these receptors (NMDA antagonists) has the same effect as alcohol

Question 21

describe the mesolimbic dopaminergic pathway (reward system of brain)

Answer 21

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

Question 22

how does alcohol cause pleasure and possible cause dependence?

Answer 22

stimulates VTA activating mesolimbic dopaminergic pathway

Question 23

how can the reward system be activated pharmacologically?

Answer 23

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

Question 24

what changes occur to compensate for CNS depression in prolonged ethanol consumption?

Answer 24

upregulation of NMDA receptors

downregulation of GABA receptors