Effect of pimozide on home cage ethanol drinking in the rat: Dependence on drinking session length

Abstract

A stimulus-fading procedure was used to initiate ethanol drinking in freefeeding Long Evans rats. During daily half-hour drinking sessions in the home cage, a combination of sucrose and ethanol was first presented to the rats; gradually the sucrose concentration was reduced and the ethanol concentration increased until after 7 weeks the rats were drinking 10% ethanol with no sucrose. After stabilization of intake, either pimozide (PIM, 0.25, 0.50 and 1.00 mg/kg) was injected 4 h before drinking sessions or ( d)-amphetamine (DEX, 0.25 and 0.50 mg/kg) was injected 15 min before sessions. The 0.50 and 1.00 mg/kg PIM doses and the 0.50 DEX dose significantly reduced intake compared to vehicle injections. In the second part of the experiment, the rats were given 24-h access to 10% ethanol and water in a two-bottle choice procedure. In this condition, 0.50 mg/kg PIM failed to reduce intake compared to vehicle. The critical difference between the two procedures seems to be that with the 30-min sessions, PIM injections were timed to have their maximal effect during testing. With 24-h sessions, decreases in intake produced by PIM could have been compensated for by increases after the drug had worn off. The hypothesis that dopamine is necessary for ethanol reinforcement receives support from the PIM effect on the 30-min sessions. The DEX effect extends the generality of our previous finding that DEX reduces ethanol-reinforced lever pressing in free-feeding rats.