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. Microinjection of physostigmine (6-37 nmol) into the caudal part of the substantia nigra pars compacta elicited a dose-dependent contralateral circling. The circling was inhibited 93 +/- 3% by the dopamine antagonist haloperidol (53 nmol) injected into the neostriatum 90 min before the injection of physostigmine (37 nmol) into the ipsilateral substantia nigra pars compacta. The effect of haloperidol was reversible, since the circling behavior was fully restored when physostigmine was applied to the same animals 24 h later. The circling was completely blocked when physostigmine (37 nmol) was applied simultaneously with the muscarinic M1 antagonist pirenzepine (2 nmol). The M2 antagonist AF-DX 116 (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 acetylcholine stimulates muscarinic and nicotinic receptors of nigrostriatal dopaminergic neurons which, in turn, increase their firing rate and cause the circling behavior. We conclude that the pedunculopontine cholinergic neurons, which innervate the substantia nigra pars compacta, modulate the motor behavior by increasing the activity of dopaminergic nigrostriatal pathway.
Góngora-Alfaro
J L
JL
Laboratorio de Patología Experimental, Universidad Autónoma de Yucatán, México.
Hernández-López
S
S
Martínez-Fong
D
D
Flores
G
G
Aceves
J
J
D000818:Animals; D002799:Cholinergic Fibers / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D006220:Haloperidol