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

The purpose of the present investigation was to determine whether administr ation of dihydropyridine-sensitive calcium channels plays a role in modulat ing the discriminative stimulus effects of ethanol. A food-reinforced opera nt 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. A fter 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 postinjcction. Complete substitution (80% or greater ethanol-appropriate responding) for ethanol by these dihydropyridine compo unds varied among subjects with dose and pretreatment time. Overall, isradi pine substituted for the discriminative stimulus effects of ethanol in the greatest percentage of animals in both training groups. However, substituti on 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 effectiv e in animals trained with 2.0 g/kg of ethanol. For the second set of experi ments, a single dose of nimodipine, nifedipine, isradipine, or (-)-BAY k 86 44 was administered before determination of the cumulative ethanol dose res ponse. Nifedipine produced a significant leftward shift and (-)-BAY k 8644 produced a significant rightward shift in the ethanol dose-response curve i n animals trained to discriminate 2.0 g/kg of ethanol from water. These res ults indicate that the administration of VGCC modulators plays an indirect role in the discriminative stimulus effects of ethanol.