Effects of nimodipine on the discriminative stimulus properties of d-amphetamine in rats.

Abstract

The discriminative stimulus (DS) properties of d-amphetamine (AMP) are thought to be mediated by enhanced release of catecholamines, which may involve neuronal calcium influx through voltage sensitive channels. The present study examined the influence of nimodipine, a calcium channel blocker, on the DS properties of AMP. Rats (N = 8) were trained to discriminate AMP (0.5 mg/kg, IP) from saline in a two-lever, food-reinforced, drug discrimination paradigm. Nimodipine alone (2.0-5.6 mg/kg, IP) did not substitute for AMP. When given in combination with AMP, 2.0 mg/kg nimodipine increased by less than 2-fold the AMP dose necessary to induce AMP-appropriate responses. Higher doses of nimodipine combined with AMP did not increase the magnitude of this effect. Nimodipine enhanced the effects of AMP on response rate. Haloperidol (0.125 mg/kg) increased by approximately 4-fold, whereas diazepam (0.5 or 1.0 mg/kg) and morphine (5.0 mg/kg) increased by approximately 2-fold the AMP dose necessary to induce AMP-appropriate responses. The interaction with AMP was associated with enhanced reduction of response rate in the tests with diazepam and morphine but not haloperidol. These results suggest that nimodipine attenuates the DS properties of AMP, probably in a non-specific way, due to the ability of nimodipine itself to induce a discriminable internal state.