Differential effects of ondansetron, haloperidol and clozapine on electrical self-stimulation of the ventral tegmental area.

The effects of 5-HT(3), receptor blockade with ondansetron (0.025-0.2mg/kg) on intracranial self-stimulation of the ventral tegmental area were compared with effects of the typical antipsychotic drug haloperidol (0.01-0.3mg/kg) and the atypical antipsychotic drug clozapine (1.25-10mg/kg). Rats were trained to self-stimulate using unipolar ventral tegmental electrodes (200µm diameter) to deliver 1s trains of 0.2ms cathodal pulses of constant current stimulation as a reinforcer. The animals were tested daily in frequency threshold tests. The frequency that maintained half maximal response rates (M50) and the maximal number of responses at a single frequency (RMAX) and the number of responses per session (TRESP) were used to measure drug effects. Ondansetron had no effects on the behavioural measures in this study. Haloperidol induced a significant increase in M50 at 0.3mg/kg without altering RMAX; TRESP was reduced by 0.1 and 0.3mg/kg of this drug. Clozapine increased M50 at 5.0mg/kg; following 10.0mg/kg of clozapine responding was completely abolished and no M50 measure could be calculated. Clozapine reduced RMAX at 1.25, 5.0 and 10.0mg/kg; TRESP was decreased by 5.0 and 10.0mg/kg of clozapine. The present results indicate that ondansetron had no measurable effects under conditions in which haloperidol and clozapine increase reinforcement thresholds and decrease response rates maintained by ventral tegmental self-stimulation.