The effects of pimozide on the reinforcing efficacy of central grey stimulation in the rat.

Abstract

The present report describes the effects of the neuroleptic pimozide on the reinforcing efficacy of central grey stimulation. Six adult rats were implanted with a monopolar moveable stimulating electrode in the pontine central grey. Each bar-press in an operant chamber delivered a 0.3-s train of cathodal rectangular pulses of constant duration (0.1 ms) and intensity (from 180 to 440 microA depending on the subject) and of variable frequency. The function relating the rate of bar-pressing to the logarithm of the number of pulses per train (rate-frequency function) was recorded following administration of vehicle and increasing doses of pimozide (from 0.15 to 0.5 mg/kg). Pimozide produced a dose-dependent parallel shift of the rising segment of the rate-frequency function towards higher pulse numbers in 4 subjects, indicating that the drug reduced the reinforcing efficacy of the stimulation. In two subjects, the shift was accompanied by a decrease in slope of the rising segment. Depending on the subject, the greatest shift observed varied from 0.087 to 0.489 log units. Further attempt to increase the magnitude of shift with higher doses resulted in complete abolition of self-stimulation. The fact that pimozide reduced the value of reward in an area containing only marginal amounts of dopaminergic cells adds support to the hypothesis that dopamine modulates reward indirectly. The fact that the shift could not be increased with higher doses was interpreted as an indication that dopaminergic neurons are involved in a gate-like synaptic arrangement in which a limited decrease in dopaminergic activity is sufficient to obliterate the transmission in the reward pathway or the conversion of the signal into a reinforcing effect.