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

Abstract

Chronic blockade of the dopamine (DA) D 2 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 D 2 antagonist, S(-)-sulpiride, also decreased nigral SP. Following blockade of the dopamine D 1 receptor by chronic administration of the selective D 1 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 D 1 or D 2 antagonist suggests that the two DA receptor subtypes exert tonic, opposing, modulatory influences on the SP content of the striatonigral pathway.