Acute changes in nigral substance P content induced by drugs acting on dopamine, muscarine and GABA receptors.

Effects of acutely administered drugs acting on dopamine, muscarine or GABA receptors on the substance P content in rat substantia nigra were examined. Systemic injection of apomorphine caused a significant reduction in the nigral substance P content. This effect was found to be partially inhibited by atropine pretreatment. Haloperidol completely abolished the effect of apomorphine, while sulpiride did not. When administered alone, haloperidol, sulpiride or atropine had no effect on the nigral substance P content. Oxotremorine, the muscarine receptor agonist, reduced substance P content in th rostral half of the substantia nigra. Reduction in the nigral substance P content was also induced by treatment with the GABA receptor antagonist picrotoxin. On the other hand, diazepam increased the substance P content. These results suggest that the striatonigral substance P neurons could be regulated by dopaminergic, cholinergic and GABAergic systems, and that the dopaminergic influence on the substantia P neurons may be mediated, at least in part, by the cholinergic system.