RELEASE AND ACCUMULATION OF NEUROTRANSMITTERS IN THE RAT-BRAIN - ACUTE EFFECTS OF ETHANOL IN-VITRO AND EFFECTS OF LONG-TERM VOLUNTARY ETHANOL INTAKE

Release from and accumulation in tissue slices of some neurotransmitte rs under acute ethanol in naive rats and in long-term voluntarily etha nol drinking rats were investigated. Slices of the rat caudatoputamen were prelabeled with [H-3]choline and release of [H-3]acetylcholine wa s stimulated through either N-methyl-D-aspartate (NMDA) receptors or s trychnine-sensitive glycine receptors. Ethanol in vitro at 2 parts per thousand, 4 parts per thousand, and 6 parts per thousand (34 mM, 68 m M, and 102 mM, respectively) concentration-dependently depressed the m aximum effect of the concentration-response curve of NMDA in naive rat s. In contrast, voluntary ethanol consumption over months led to a sig nificantly enhanced NMDA receptor response characterized by an increas e in the maximum effect of the concentration-response curve. The glyci ne receptor-mediated release of [H-3]acetylcholine, which is inhibited by acute ethanol in a competitive-like fashion, was not changed in an imals that ingested ethanol over months. Electrically evoked release o f [H-3]noradrenaline ([H-3]NA) and its presynaptic modulation by morph ine through mu-opioid receptors in neocortical slices of the rat, prel oaded with [H-3]NA, was nearly identical in both ethanol-naive rats an d in ethanol drinking rats. The accumulation of [H-3]gamma-aminobutyri c acid in rat cerebellum tissue was neither affected by acute ethanol in vitro nor after chronic ethanol consumption. In summary, long-term voluntary ethanol intake caused a significant increase in NMDA recepto r function in the rat caudatoputamen, but did not result in changes in glycine-evoked [H-3]acetylcholine release of electrically evoked [H-3 ]NA release modulated by morphine or cerebellar [H-3]gamma-aminobutyri c acid accumulation.