Effects of pimozide on positive and negative incentive contrast with rewarding brain stimulation.

Positive and negative contrast effects with brain-stimulation reward were inferred from significant differences in rate/intensity curves obtained by ascending, random and descending orders of current presentation. The neuroleptic drug pimozide caused a dose-related attenuation of both positive and negative contrast. A dose of 0.1 mg/kg blocked positive contrast obtained by comparing ascending and random rate/intensity curves. Negative contrast and threshold current intensities for brain-stimulation reward at sites in the ventral tegmental area were unaffected by the low dose (0.1 mg/kg) of pimozide. Higher doses of pimozide (0.25, 0.4 mg/kg) blocked both positive and negative contrast effects, and caused a significant elevation in threshold current intensities under the random order condition. Two doses (0.25, 0.4 mg/kg) of pimozide were associated with performance deficits as the response rates at the maximum current intensities were attenuated significantly with each order of current presentation. These demonstrations of both positive and negative contrast are consistent with the theoretical position linking brain-stimulation reward to incentive motivation. Furthermore the effects of the dopamine receptor antagonist pimozide are consistent with a role for dopamine in brain-stimulation reward and also raise the possibility of dopaminergic involvement in incentive contrast phenomena.