Quantitative radioimmunocytochemical evidence that haloperidol and SCH 23390 induce opposite changes in substance P levels of rat substantia nigra.

Chronic blockade of the dopamine (DA) D2 receptor by repeated systemic administration of the butyrophenone neuroleptic, haloperidol (HAL), is known to lead to a decrease in levels of the neuroactive peptide, substance P (SP), in the rat striatum and substantia nigra (SN). Using a high-resolution, quantitative radioimmunocytochemistry (RIC) technique, we have shown the HAL-induced decrease in rat nigral SP to be both dose- and time-dependent. In addition, chronic administration of the highly selective D2 antagonist, S(-)-sulpiride, also decreased nigral SP. Following blockade of the dopamine D1 receptor by chronic administration of the selective D1 antagonist, SCH 23390, we found, in contrast, that levels of SP in SN were increased in a dose- and time-dependent fashion. The magnitude of the maximum SCH 23390-induced elevation (20-30%) of nigral SP was approximately equal to that of the maximum HAL-induced decrease. The opposite response of nigral SP levels to repeated injections of a D1 or D2 antagonist suggests that the two DA receptor subtypes exert tonic, opposing, modulatory influences on the SP content of the striatonigral pathway.