REGULATION OF TRANSMITTER SYNTHESIS AND RELEASE IN MESOLIMBIC DOPAMINERGIC NERVE-TERMINALS - EFFECT OF ETHANOL
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1981
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Abstract
Slices from rat olfactory tubercle were incubated in freshly oxygenated Krebs-Ringer phosphate (KRP) and in the presence of L-tyrosine[14C-U [uniformly 14C-labeled]] as dopamine (DA) precursor. The newly synthesized [14C]DA and the [14C]DA released into the incubation media were isolated by Alumina column and ion-exchange chromatography. The presence of K+ depolarizing concentrations (25-70 mM) in the incubation media markedly increased the formation of [14C]DA from [14C]tyrosine, following a rather complex and biphasic pattern. Dibutyryl cAMP (dB-cAMP) and theophylline increased the formation of newly synthesized [14C]DA. Ethanol (0.2 to 0.4%, wt/vol) significantly blocked the stimulation of [14C]DA biosynthesis that was induced by low K+ depolarizing concentrations (25 mM) and by dB-cAMP (5 .times. 10-4 M) or theophylline (1 .times. 10-3 M. Only higher ethanol concentrations (0.8 to 1.1%, wt/vol) blocked the increase in DA formation induced by high K+ depolarizing concentrations (40 and 55 mM). K depolarization (40 mM) markedly evoked the release of newly synthesized [3H]DA or [3H]DA previously taken up by the slices. The release was dependent upon the presence of Ca2+ and inhibited by an excess of Mg2+ (12 mM). Ethanol (0.8-1.1%, wt/vol) produced no effect on K+-induced release of [3H]DA. The model described can be used as a simple experimental tool to study neurotransmitter synthesis and release from nerve terminals belonging to the mesolimbic dopaminergic system. At least 2 mechanisms exist by which neuronal depolarization increases transmitter formation in mesolimbic dopaminergic terminals. Ethanol, at relatively low concentrations, seems to produce a specific inhibitory effect upon the mechanism that predominates under low depolarizing conditions. The possibility is raised that the effects described for ethanol may play a role in the neuropharmacological responses induced by this agent in vivo.