This study is intended to help elucidate interactions which take place between neuronal systems within the basal ganglia, the site for control of mental states and locomotion. I have previously demonstrated that drug-induced variations in the activity of the nigral-striatal dopamine pathway (i.e., following the administrations of amphetamine, haloperidol and nigral injections of 6-hydroxydopamine) result in changes in the levels of substance P-like immunoreactivity (SPLI) within the substantia nigra. These changes in nigral SPLI are likely caused by variations in the activity of the striatal-nigral substance P neurons and demonstrate that this feedback pathway is at least partially controlled by dopaminergic influence. The possibility exists that other neuronal systems are also involved in this interaction between the dopaminergic and substance P pathways. For example, it has been suggested that dopaminergic influences on the substance P system are mediated through a cholinergic link. The studies outlined in this proposal are designed to test this hypothesis. This will be accomplished by administering cholinergic agonists (pilocarpine and physostigmine) and antagonist (atropine) with the dopaminergic agents mentioned above. The changes in nigral SPLI levels following these drug treatments will be monitored. If the striatal cholinergic system functions as a neuronal connection between the dopamine and substance P pathways one would expect the presence of the cholinergic drugs to alter the pattern of change in nigral SPLI levels induced by the dopamine-active drugs. Positive results would support a role for cholinergic neurons in the regulation of the nigral-striatal dopamine pathway through striatal-nigral feedback loops.