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 neurotransmitters under acute ethanol in naive rats and in long-term voluntarily ethanol drinking rats were investigated. Slices of the rat caudatoputamen were prelabeled with [³H]choline and release of [³H]acetylcholine was stimulated through either N -methyl- d -aspartate (NMDA) receptors or strychnine-sensitive glycine receptors. Ethanol in vitro at 2%, 4%, and 6% (34 mM, 68 mM, and 102 mM, respectively) concentration-dependently depressed the maximum effect of the concentration-response curve of NMDA in naive rats. In contrast, voluntary ethanol consumption over months led to a significantly enhanced NMDA receptor response characterized by an increase in the maximum effect of the concentration-response curve. The glycine receptor-mediated release of [³H]acetylcholine, which is inhibited by acute ethanol in a competitive-like fashion, was not changed in animals that ingested ethanol over months. Electrically evoked release of [³H]noradrenaline ([³H]NA) and its presynaptic modulation by morphine through μ-opioid receptors in neocortical slices of the rat, preloaded with [³H]NA, was nearly identical in both ethanol-naive rats and in ethanol drinking rats. The accumulation of [³H]γ-aminobutyric 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 receptor function in the rat caudatoputamen, but did not result in changes in glycine-evoked [³H]acetylcholine release of electrically evoked [³H]NA release modulated by morphine or cerebellar [³H]γ-aminobutyric acid accumulation.