Antagonism of ethanol's central stimulation by catecholamine receptor agonists.
The effect of ethanol (2 g/kg) on brain catecholamine neurons in the rat as well as its interaction with catecholamine receptor agonists was studied utilizing single unit recording techniques. Identified dopamine (DA) neurons of the zona compacta, substantia nigra as well as noradrenaline (NA) neurons of the locus coeruleus showed no alterations in firing rate at ethanol administration. Also the function of their presynaptic DA and NA receptors, respectively, appeared normal judging from the unaltered inhibitory response to systemically or microiontophoretically applied receptor agonists, apomorphine and clonidine, respectively, when applied in small doses. In contrast, the catecholamine releasing agent amphetamine caused inhibition of firing of the central catecholamine neurons in the same anesthetized preparation. The rate of tryosine hydroxylation in vivo in central DA and NA neurons measured as the amount of Dopa accumulated in various brain regions following inhibition of aromatic l-amino acid decarboxylase by NSD 1015, 150 md/kg i.p., was significantly increased by ethanol in anesthetized rats. Consequently, the present data do not support the hypothesis derived largely from behavioural evidence that ethanol causes inactivation of central DA and NA neurons. The antagonism by catecholamine receptor agonists, apomorphine and clonidine of ethanol's behaviourally stimulant action may thus be of unspecific character. The results indicate that alterations in tyrosine hydroxylase activity, when measured as Dopa formation after decarboxylase inhibition, can occur without concomitantly altered impulse activity in central DA or NA neurons. At present the action of ethanol on brain DA and NA neurons remains unclear and necessitates further studies.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001592:Benzyl Alcohols / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009928:Organ Specificity; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*
D001592:Benzyl Alcohols; D002395:Catecholamines; D006834:Hydrazines; D011955:Receptors, Drug; D000431:Ethanol; D004295:Dihydroxyphenylalanine; C004297:3-hydroxybenzylhydrazine; D003000:Clonidine; D001058:Apomorphine; D003913:Dextroamphetamine