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ME Risner, SR Goldberg, JA Prada and EJ Cone
The behavioral effects of nicotine were compared with those of its metabolites, nornicotine and cotinine, in beagle dogs and squirrel monkeys. Subjects responded under a multiple fixed-interval (FI) 300- sec, fixed-ratio (FR) 30 response schedule of food presentation. Nicotine (0.01-1.0 mg/kg i.m.) and nornicotine (0.03-3.0 mg/kg i.m.) produced qualitatively similar effects in both dogs and monkeys. Nicotine produced dose-related increases, then decreases in rates of responding during FI components; rates of responding during FR components were only decreased. Nornicotine produced only dose- dependent decreases in responding during both FI and FR components. In the dogs, cotinine (0.01-10.0 mg/kg i.m.) produced only dose-dependent decreases in rates of responding during both FI and FR components. In the squirrel monkeys, however, cotinine (0.1-3.0 mg/kg i.m.) increased responding during FI components; a high dose of 30.0 mg/kg decreased responding during both FI and FR components. The behavioral effects of cocaine (0.03-3.0 mg/kg i.m.) and its metabolite norcocaine (0.01-1.0 mg/kg i.m.) were compared in the dogs. FI rates of responding first increased and then decreased with increasing doses of each drug, whereas FR rates of responding only decreased in a dose-related manner. Norcocaine was slightly more potent than cocaine in producing these effects on schedule-controlled responding in dogs. These experiments indicate the metabolites of nicotine and cocaine are behaviorally active and may contribute to the pharmacological profile of the parent compounds.
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L. P. Dwoskin, L. Teng, S. T. Buxton, and P. A. Crooks (S)-(-)-Cotinine, the Major Brain Metabolite of Nicotine, Stimulates Nicotinic Receptors to Evoke [3H]Dopamine Release from Rat Striatal Slices in a Calcium-Dependent Manner J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 905 - 911. [Abstract] [Full Text]
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P. A. Crooks, M. Li, and L. P. Dwoskin Metabolites of Nicotine in Rat Brain After Peripheral Nicotine Administration. Cotinine, Nornicotine, and Norcotinine Drug Metab. Dispos., January 1, 1997; 25(1): 47 - 54. [Abstract] [Full Text]
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