CIRCLING BEHAVIOR ELICITED BY CHOLINERGIC TRANSMISSION IN THE SUBSTANTIA-NIGRA PARS COMPACTA - INVOLVEMENT OF NICOTINIC AND MUSCARINIC RECEPTORS

The influence of cholinergic transmission within the substantia nigra pars compacta on circling behavior was assessed in male rats. Microinj ection of physostigmine (6-37 nmol) into the caudal part of the substa ntia nigra pars compacta elicited a dose-dependent contralateral circl ing. The circling was inhibited 93 +/- 3% by the dopamine antagonist h aloperidol (53 nmol) injected into the neostriatum 90 min before the i njection of physostigmine (37 nmol) into the ipsilateral substantia ni gra pars compacta. The effect of haloperidol was reversible, since the circling behavior was fully restored when physostigmine was applied t o the same animals 24 h later. The circling was completely blocked whe n physostigmine (37 nmol) was applied simultaneously with the muscarin ic M(1), antagonist pirenzepine (2 nmol). The M(2) antagonist AF-DX 11 6 (2 nmol) only partially blocked the circling induced by a lower dose of physostigmine (12 nmol). The nicotinic antagonist mecamylamine (5 nmol) also inhibited the circling, but only during the 5 min following co-injection of the drugs. These results indicate that endogenous ace tylcholine stimulates muscarinic and nicotinic receptors of nigrostria tal dopaminergic neurons which, in turn, increase their firing rate an d cause the circling behavior. We conclude that the pedunculopontine c holinergic neurons, which innervate the substantia nigra pars compacta , modulate the motor behavior by increasing the activity of dopaminerg ic nigrostriatal pathway.