The effect of ethanol on GABAergic transmission.
One of the many actions of ethanol involves the GABAergic system. The interaction of ethanol with GABAergic neurons is a complex one involving both presynaptic and postsynaptic sites. Through a presumed fluidization of membranes after a single dose of ethanol, the available in vitro evidence suggests that ethanol disrupts the normal functioning of the GABA-benzodiazepine-chloride ionophore complex in a complicated manner involving a sequential activation of different active sites leading to the facilitation of GABA transmission. This finding has been supported in vivo using electrophysiological techniques. Presynaptic GABAergic neurons may experience a reduced activity, especially at low doses of ethanol. After chronic ethanol treatment, GABAergic transmission may be reduced, especially during an ethanol withdrawal syndrome. Also, other changes in the GABA-benzodiazepine-chloride ionophore complex suggest GABA transmission is suppressed postsynaptically. Drugs which enhance the actions of GABA may be suitable inhibitors of the ethanol withdrawal syndrome. In particular a new class of drugs, the triazolopyridazines, may be promising compounds for treatment of withdrawal with a more specific mode of action and fewer side effects.
D000430:Alcohol Withdrawal Delirium / Q000188:drug therapy / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D001569:Benzodiazepines; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D009474:Neurons / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011963:Receptors, GABA-A; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000431:Ethanol; D005680:gamma-Aminobutyric Acid