Kl. Green et Ka. Grant, Effects of L-type voltage-sensitive calcium channel modulators on the discriminative stimulus effects of ethanol in rats, ALC CLIN EX, 23(5), 1999, pp. 806-814
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.