EFFECTS OF NICOTINE ON FIXED-INTERVAL BEHAVIOR AND THEIR MODIFICATION BY CHOLINERGIC ANTAGONISTS

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

The effects of nicotine were studied on operant responding maintained in rats by a fixed-interval 88-second schedule of water reinforcement. Nicotine was administered immediately prior to the experimental session in doses of 0.05 to 0.4 mg/kg s.c. The drug produced an initial cessation of responding, the duration of which was dose-related. The length of this depression initially decreased over successive injections of 0.4 mg/kg of nicotine. After the initial depression, local rates of fixed-interval responding were altered during nicotine sessions. Base-line rates below 20 responses/min were variably affected; whereas, rates above 30 responses/min were reliably depressed. The degree of rate depression was dose-related. The actions of nicotine, 0.4 mg/kg, were compared to those of d-amphetamine, 0.4 mg/kg. At the comparison dose, nicotine produced more depression of high rates than did d-amphetamine; whereas, d-amphetamine was more effective in elevating low rates than was nicotine. Cholinergic antagonists were used to demonstrate the specificity of the response to nicotine. It was concluded that drug-induced initial depression and response rate depression were due to a nicotinic cholinergic action. The rate stimulation induced by nicotine was not consistently blocked by nicotinic antagonists.

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