The effect of chronic ethanol administration on central neurotransmitter mechanisms.
Rats were maintained on ad lib food and a forced-intake regimen of ehtanol for up to 270 days. The ethanol treatment induced alterations in the metabolism of central catecholamines seen as increased endogenous concentrations of dopamine concomitantly with decreased concentrations of noradrenaline in the limbic forebrain. The synthesis of catecholamines, measured as the accumulation of dopa following inhibition of aromatic amino acid decarboxylase, was unchanged during chronic ethanol treatment. Local application of dopamine into the nucleus accumbens caused a greater increase in locomotor activity in chronic ethanol rats than in controls thus indicating that chronic ethanol treatment increased the sensitivity at or beyond central dopamine receptors. This phenomenon of functional dopamine receptor supersensitivity was first observed after 5 months of ethanol treatment and lasted for about 4 weeks after cessation of the ethanol treatment. The sensitivity of noradrenergic and cholinergic receptor mechanisms appeared to be unchanged after chronic exposure to ethanol. The effect of the GABAergic drug, gamma-butyrolactone (GBL) on the accumulation of dopa after inhibition of aromatic amino acid decarboxylase was studied in chronic ethanol rats. The enhancement of the dopa formation in dopaminergic neurons induced by GBL was markedly attenuated after chronic ethanol treatment. The gross behavioural depression by GBL was also weakened. This may indicate that chronic ethanol treatment causes subsensitivity of GABA receptors.
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000096:biosynthesis; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D013375:Substance Withdrawal Syndrome; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
D002395:Catecholamines; D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D004295:Dihydroxyphenylalanine; D011433:Propranolol; D001142:Aromatic-L-Amino-Acid Decarboxylases; D015107:4-Butyrolactone; D004298:Dopamine; D009638:Norepinephrine