Potential serotonergic interactions with the anxiolytic-like effects of calcium channel antagonists

In a series of experiments, we investigated the interaction between the calcium channel antagonist, nifedipine, and the 5-HT1A agonist, ipsapirone. In the first experiment, we demonstrated that nifedipine (20 mg/kg), and to a lesser extent nimodipine (20 mg/kg), exerted an anxiolytic-like effect as did diazepam (5 mg/kg) in an experimental paradigm based on water consumption in a novel environment. In the second experiment, nifedipine (1.25, 2.5, and 5 mg/kg), and in the third experiment, ipsapirone (1.5. 3.0, and 6.0 mg/kg), have been found to exert a dose-dependent effect in the same test. Finally, a small and ineffective dose of ipsapirone (1.5 mg/kg) potentiated the anxiolytic-like effect of various doses of nifedipine. The data obtained are discussed in terms of the potential anxiolytic-like action of calcium channel antagonists and in relation to their electrophysiological effects. Moreover, the interaction between ipsapirone and nifedipine is discussed in terms of the possible involvement of central serotonergic systems in the behavioral effects of the calcium channel antagonists.