Behavioral effects of nicotine: schedule-controlled responding by squirrel monkeys
Spealman, R.D.; Goldberg, S.R.; Gardner, M.L.
Journal of Pharmacology and Experimental Therapeutics 216(3): 484-491
1981
ISSN/ISBN: 0022-3565 PMID: 7205628 Document Number: 174920
Nicotine is a naturally-occurring alkaloid found in tobacco leaves and is one of the drugs most frequently used by man, primarily in inhaled tobacco smoke. The behavioral effects of nicotine were compared with those of d-amphetamine. Squirrel monkeys responded by pressing a lever under a multiple fixed-interval, fixed-ratio schedule of either presentation of food or termination of a stimulus associated with electric shock (stimulus-shock termination). The effects of the drugs depended primarily on the type of component schedule (fixed-interval; fixed-ratio) that maintained responding. As the dose of nicotine (0.01-3.0 mg/kg) or d-amphetamine (0.01-1.0 mg/kg) was increased, overall responding in the fixed-interval component first increased and then decreased, whereas overall responding in the fixed-ratio component decreased in a dose-related manner. Both drugs altered the temporal pattern of responding in the fixed-interval component. Doses that produced peak increases in overall responding increased the low response rates at the beginning of the interval more than the higher response rates at the end of the interval; the increases in responding were characteristically greater with d-amphetamine than with nicotine regardless of the control response rate. The effects of the drugs were largely independent of the type of consequent event (food presentation; stimulus-shock termination) that maintained responding, but high doses of either drug produced more pronounced decreases in responding under the multiple schedule of food presentation than under the multiple schedule of stimulus-shock termination. The behavioral effects of nicotine were blocked by the centrally acting nicotinic antagonist, mecamylamine (0.1-1.0 mg/kg) but not by the peripherally acting nicotinic antagonist, hexamethonium (1.0-10.0 mg/kg). Nicotine and d-amphetamine had qualitatively similar effects on schedule-controlled behavior, but nicotine had a more rapid onset of action, a shorter duration of action and was less effective than d-amphetamine in increasing responding.