Drug-induced depression of gamma efferent activity—II. Central action of nicotine

Abstract

Nicotine, which produces a generalized depression of spontaneous γ efferent activity by reflex action in the cat under chloralose-urethane anesthesia, has now been shown to be capable of affecting γ discharge also by a central action. The evidence for this central action is threefold. First, there is a hexamethonium-resistent component of nicotine-induced γ depression after intravenous injection of doses above 80 μg/kg, whereas the γ depressant effect of sebacylcholine, a peripherally acting nicotinic stimulant, could always be blocked by hexamethonium. Second, nicotine elicits γ depression when injected into the lateral ventricle of the brain in amounts of 1–5 μg/kg. Third, this effect, elicited from a yet unspecified region bordering the ventricular space, yields to blockade by the centrally acting nicotine antagonist mecamylamine given by either route, but persists in presence of peripheral nicotine block induced by hexamethonium. The γ depression ensuing upon intracerebroventricular injection resembled that following intravenous injection of nicotine. It was often preceded by brief acceleration and occurred bilaterally in extensor as well as flexor fibers. With the fusimotor innervation intact, spindle afferent discharge paralleled the changes in γ activity. Both the dynamic and static responses of group Ia units were reduced during the γ depression. The central site of the γ depressant effect of nicotine must differ from that of chlorpromazine, since chlorpromazine still depressed γ firing when the nicotine effect was abolished by mecamylamine. Both nicotinic and muscarinic cholinergic antagonists left spontaneous γ activity unaffected, indicating that the neurocircuits sustaining this activity have no cholinergic neurons. Cholinergic mechanisms, on the other hand, may be involved in the central control of γ discharge, as the centrally induced γ depression after nicotine injection does suggest.