CHOLINERGIC STIMULATION OF ROSTRAL AND CAUDAL SUBSTANTIA-NIGRA PARS COMPACTA PRODUCES OPPOSITE EFFECTS ON CIRCLING BEHAVIOR AND STRIATAL DOPAMINE RELEASE MEASURED BY BRAIN MICRODIALYSIS

Turning in circles is among the behaviors elicited by unilateral choli nergic stimulation of the substantia nigra. Recent studies have shown that microinjection of cholinergic agonists into the substantia nigra pars compacta increases dopamine release and turnover in the striatum of anesthetized rats [Hernandez-Lopez et al. (1992) Brain. Res. 598, 1 14-120; Blaha and Winn (1993) J. Neurosci. 13, 1035-1044]. In this stu dy, the relationship between circling behavior and striatal dopamine r elease following cholinergic stimulation of the substantia nigra pars compacta neurons was assessed by brain microdialysis in awake rats. Th e results indicate that cholinergic stimulation of the substantia nigr a pars compacta with the mixed nicotinic-muscarinic cholinergic agonis t carbachol modulates striatal dopamine release, and this effect is ac companied by circling behavior and stereotypies. Microinjection of car bachol (109 nmol) in the caudal portions of the substantia nigra pars compacta induced contralateral circling associated with an increase of dopamine release in neostriatum. On the contrary, ipsilateral circlin g and reduction of striatal dopamine release was elicited when the sam e dose of the drug was applied in the rostral portions of the substant ia nigra pars compacta. The above findings are in accordance with rece nt electrophysiological studies suggesting the existence of sub-popula tions of nigrostriatal dopaminergic neurons, and indicate that the sub stantia nigra pars compacta is functionally compartmentalized. We conc lude that the cholinergic input to the substantia nigra pars compacta could modulate the motor behavior through regulating the firing rate o f nigrostriatal dopaminergic neurons and dopamine release in the neost riatum.