COMPARISON OF MUSCARINIC AND NICOTINIC CHOLINERGIC AGONISTS ON SELF-STIMULATION BEHAVIOR

¹ Michigan Neuropsychopharmacology Research Program, Department of Pharmacology, University of Michigan, Ann Arbor, Michigan

The effects of cholinergic agonists and antagonists were investigated on self-stimulation in rats with chronically implanted elcetrodes in the lateral posterior hypothalamus. Physostigmine (50-300 µg/kg s.c.) caused depression of self-stimulation. The magnitude, lateney and duration of this effect were dose-related. Arecoline (100-3000 µg/kg s.c.) had similar actions, but the depression was less dramatic and of shorter duration. Nicotine (25-600 µg/kg s.c.) caused biphasic effects; the initial depression was sometimes followed by facilitation, and the actions were much less consistent. The depressant effects of physostigmine and arecoline were blocked by scopolamine (0.5 mg/kg) and enhanced by mecamylamine (5.0 mg/kg). Methscopolamine (0.5 mg/kg) and trimethidinium (5.0 mg/kg) were much less effective. The results suggest that muscarinic cholinergic agonists which penetrate the blood-brain barrier depress self-stimulation on a central basis, whereas nicotinic cholinergic agonists have complex depressant and stimulant effects of both central and peripheral origin.

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