Effects of calcium channel blockers on behaviors induced by the N-methyl-D-aspartate receptor antagonist, dizocilpine, in rats

The present study assessed the ability of voltage-sensitive calcium channel (VSCC) blockers to affect the behavioral effects of the noncompetitive N-m ethyl-D-aspartate (NMDA) receptor antagonist, dizocilpine, in male Wistar r ats. Dizocilpine produced dose-dependent increases in locomotor activity. N imodipine, verapamil, and flunarizine suppressed dizocilpine-facilitated ve rtical activity, while horizontal activity was attenuated by verapamil and nimodipine but not flunarizine. Repeated dizocilpine injections resulted in the development of sensitization to its locomotor stimulating properties. Development of sensitization was not context specific, and was observed fol lowing repeated exposures to 0.1 but not 0.056 or 0.3 mg/kg of dizocilpine. Nimodipine retarded the development of sensitization to dizocilpine's stim ulating effects on horizontal activity, while verapamil suppressed sensitiz ation to the vertical stimulating effects of dizocilpine. Flunarizine had n o significant effects on sensitization to dizocilpine's locomotor stimulati ng properties. In rats trained to discriminate between injections of 0.056 mg/kg of dizocilpine and vehicle, none of the tested VSCC blockers was able to completely antagonize the discriminative stimulus properties of dizocil pine. Nimodipine, when administered in combination with the training dose o f dizocilpine, modestly decreased the dizocilpine-lever selection. Dizocilp ine dose dependently decreased the self-determined stimulation threshold im planted in rats with electrodes into the ventral tegmental area. Nimodipine exhibited some tendency to block the facilitating effects of dizocilpine, while verapamil and flunarizine had no effects. In summary, in the present experiments VSCC blockers exerted only modest interactions with the behavio ral effects of dizocilpine, and it is unlikely that VSCC blockers have rema rkable potential as adjunct treatment aimed at correcting the negative side effects of NMDA receptor antagonists (e.g., dizocilpine). (C) 1999 Elsevie r Science Inc.