Voluntary ethanol consumption decreases after the inactivation of central acetaldehyde by d-penicillamine

Acetaldehyde, the first metabolite of ethanol, may mediate some ethanol-induced effects. Previous research in our laboratory has shown that d-penicillamine, an inactivation agent for acetaldehyde, is effective in decreasing locomotor stimulation and conditioned place preference induced by ethanol in mice. In the present study, the effects of d-penicillamine on the voluntary consumption of ethanol were assessed. Male rats were offered ethanol under restricted access, without food or water deprivation. Daily availability of ethanol was limited to a 15-min period in the home cages. When the response for 10% ethanol was stable, rats received an intraperitoneal (IP) injection of d-penicillamine (0, 25, 50 or 75 mg/kg) over a 5-day period, given 30 min before exposure to ethanol. In a second study we determined the specificity of d-penicillamine effects (50 mg/kg) on voluntary sucrose consumption (3%). Another study was conducted to evaluate whether IP d-penicillamine (50 mg/kg) alters taste reactivity responses. In the final experiment, rats were treated with intracerobroventricular (ICV) infusions of d-penicillamine (75 μg) for 5 days before drinking ethanol or sucrose. d-Penicillamine was found to reduce ethanol intake in a dose-dependent manner. Sucrose consumption was also affected by this thiol amino acid. We also demonstrated that d-penicillamine produced changes in the ingestive and flavor properties of sucrose and ethanol, measured by means of a taste reactivity test. When d-penicillamine was administered ICV, only voluntary ethanol consumption was modified. These findings indicate that the central inactivation of acetaldehyde blocks ethanol intake in rats, and suggest that acetaldehyde plays a key role in the motivational properties of ethanol.