Effects of L-type voltage-sensitive calcium channel modulators on the discriminative stimulus effects of ethanol in...

The purpose of the present investigation was to determine whether administration of dihydropyridine-sensitive calcium channels plays a role in modulating the discriminative stimulus effects of ethanol. A food-reinforced operant methodology was used to train adult male Long-Evans rats to discriminate either 1.0 g/kg of ethanol from water or 2.0 g/kg of ethanol from water. After training, two sets of experiments were conducted. First, a time course procedure was implemented whereby a single intraperitoneal dose of either nimodipine (3, 10, 30 mg/kg), nifedipine (3, 10, 30 mg/kg), or isradipine (1, 3, 10, 17 mg/kg) was administered, and test sessions were conducted 10, 20, 30, 60, and 90 min postinjection. Complete substitution (80% or greater ethanol-appropriate responding) for ethanol by these dihydropyridine compounds varied among subjects with dose and pretreatment time. Overall, isradipine substituted for the discriminative stimulus effects of ethanol in the greatest percentage of animals in both training groups. However, substitution varied with dose. Nifedipine dose dependently substituted for ethanol in half of the animals trained with 1.0 g/kg of ethanol but was less effective in animals trained with 2.0 g/kg of ethanol. For the second set of experiments, a single dose of nimodipine, nifedipine, isradipine, or (-)-BAY k 8644 was administered before determination of the cumulative ethanol dose response. Nifedipine produced a significant leftward shift and (-)-BAY k 8644 produced a significant rightward shift in the ethanol dose-response curve in animals trained to discriminate 2.0 g/kg of ethanol from water. These results indicate that the administration of VGCC modulators plays an indirect role in the discriminative stimulus effects of ethanol.