Non-selective enhancement of locus coeruleus and substantia nigra self-stimulation after termination of chronic dopaminergic receptor blockade with pimozide in rats.

Abstract

Self-stimulation of substantia nigra and locus coeruleus were assessed before and after an 8-day regimen in which pimozide was given twice daily at a dose of 0.5 mg/kg (first 4 days) or 1.0 mg/kg (last 4 days). At 48 hours after termination of pimozide treatment self-stimulation was increased to 25% above pre-pimozide baseline levels: this was true for both self-stimulation sites. Rates remained high the following day but returned to normal by the third day of post-pimozide-testing. These data are interpreted as reflecting pimozide-induced supersensitivity in a dopamenergic substrate. This substrate appears to be critical for intracranial self-stimulation even when its fibers are not themselves activated at the tip of the stimulating electrode.