Acetaldehyde sequestration by D-penicillamine prevents ethanol relapse-like drinking in rats: evidence from an operant self-administration paradigm.

Previous experiments in our laboratory have shown that D-penicillamine (DP) (acetaldehyde sequestering agent) is able to block the increase in ethanol consumption observed after a period of imposed deprivation (the so-called alcohol deprivation effect (ADE)), using a non-operant paradigm in Wistar rats. This study is aimed at investigating the robustness and reproducibility of our previous data using an operant paradigm, which is considered to be a valid and reliable model of human drug consumption, and the ADE, probably the most often used measure of ethanol relapse-drinking behaviour in rats. Male Wistar rats with a limited (30-min sessions), intermittent and extended background of ethanol operant self-administration were used. In order to evaluate the efficacy of several DP doses (6.25, 12.5 and 25 mg/kg i.p.) in preventing alcohol relapse, we set up a protocol based on the ADE. In a separate experiment, the effect of DP on spontaneous motor activity of rats was also tested. A significant ADE was observed in animals treated with saline. DP treatment blocked the increase in ethanol responses following the imposed abstinence period. The higher dose suppressed the ADE and provoked a significant reduction in ethanol consumption with respect to the baseline conditions. Basal motor activity was not altered after DP treatment. Our positive results with DP, using two different paradigms that evaluate relapse of ethanol drinking, will help to increase the positive predictive value of pre-clinical experiments and offer a solid base to inspire human studies with DP.