Discriminative stimulus properties of isradipine: Effect of other calcium channel blockers

Abstract

This study constitutes the first report of a calcium channel blocker used as a drug capable of controlling differential responding in a drug-discrimination paradigm. Male Sprague-Dawley rats were trained to discriminate between intraperitoneally administered 10.0 mg/kg isradipine and its vehicle in a two-lever, food-motivated, operant task. Once trained, rats displayed a dose-related decrease in discriminative responding when tested with lower isradipine doses. An analysis of the dose-response curve indicated an ED 50 = 5.71 mg/kg. As all training and dose-response testing occurred at 60 min postadministration, experiments were conducted with varying injection-to-test intervals ranging from 15–240 min. Results indicate that the optimum time for discriminative performance was at the time used in training, and that discrimination returned to nondrug (vehicle) levels 2 h postinjection. Administration of other L-type calcium channel blockers, viz., nifedipine (5–50 mg/kg), diltiazem (10–60 mg/kg), or nicardipine (0.5–3.0 mg/kg), as well as a novel antipsychotic that inhibits dopamine release (10–30 mg/kg of CGS 10746B), did not produce isradipine-like discriminative effects. Thus, there was no generalization from the training dose of 10 mg/kg isradipine to any of these other agents, and the results are discussed in light of the possible specificity of the isradipine discriminative stimulus cue as it is produced in the central nervous system.