Effects of chronic treatment with bupropion on self-administration of nicotine + cocaine mixtures in nonhuman primates.

Fernando B de Moura, Claire E Barkin, Bruce E Blough, F Ivy Carroll, Nancy K Mello, Stephen J Kohut

Experimental and clinical psychopharmacology 2020 Oct

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Chronic health problems associated with long-term nicotine use are the leading cause of preventable death in the United States. The use of tobacco products is 3-4 times greater among individuals with cocaine use disorder than that observed in the general population. This may reflect the propensity of nicotine to augment the reinforcing effects of cocaine. However, the mechanism of action of nicotine differs from that of cocaine, which presents a significant challenge for the development of pharmacotherapeutic interventions for the management of nicotine + cocaine polydrug abuse. Bupropion, an FDA-approved smoking cessation aid, has pharmacological actions at both monoamine transporters and nicotinic receptors, suggesting that it may be effective at decreasing nicotine + cocaine coabuse. Here, rhesus monkeys (n = 4) responded for food pellets and, separately, intravenous injections of nicotine, cocaine, or nicotine + cocaine mixtures under a second-order FR2(VR16:S) schedule of reinforcement during 7- to 10-day continuous treatment with saline or bupropion (1.0 and 1.8 mg/kg/hr). Results show that bupropion treatment dose-dependently decreased self-administration of nicotine combined with a low dose of cocaine (0.0032 mg/kg/inj); however, when the dose of cocaine in the mixture was higher (i.e., 0.01 mg/kg/inj), bupropion attenuated self-administration in only a subset of subjects. The effective dosage of bupropion increased responding for cocaine alone, nicotine alone, and for saline injections and significantly increased measures of daily activity. The apparent stimulant-like effects of bupropion at the dosage required to decrease cocaine + nicotine self-administration does not support its clinical use for the management of nicotine + cocaine polydrug abuse. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Citation

Fernando B de Moura, Claire E Barkin, Bruce E Blough, F Ivy Carroll, Nancy K Mello, Stephen J Kohut. Effects of chronic treatment with bupropion on self-administration of nicotine + cocaine mixtures in nonhuman primates. Experimental and clinical psychopharmacology. 2020 Oct;28(5):517-526