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

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).

Effects of lorcaserin (Belviq®) on nicotine- and food-maintained responding in non-human primates.

BACKGROUND: Accumulating evidence suggests that the FDA-approved serotonin 5-HT2C receptor agonist, lorcaserin (Belviq®), may be a promising candidate for the management of substance use disorders, including nicotine addiction. The present study was conducted to determine the efficacy and selectivity of acute or continuous lorcaserin treatment for decreasing the reinforcing effects of nicotine in a primate species. METHODS: Adult rhesus monkeys (n=4) with a history of nicotine self-administration (>2years) responded for injections of nicotine (0.32-100µg/kg IV) or food pellets under a fixed-ratio schedule of reinforcement during daily 100-min sessions. When responding was stable, lorcaserin was administered either as an acute pretreatment (0.1-1.0mg/kg, IM) or by continuous infusion (0.1mg/kg/hr, SC for 3-5days). Daily activity patterns were also monitored immediately following experimental sessions. RESULTS: Results indicate that acute lorcaserin pretreatment produced significant and dose-dependent decreases in nicotine-maintained responding across a >100-fold range of self-administered nicotine doses. Continuous lorcaserin treatment decreased intake of 10µg/kg/inj nicotine to about 50% of baseline values. Food-maintained responding was only moderately decreased in 3 of 4 subjects after acute administration and unaffected in all subjects during continuous treatment. Daily activity also was significantly decreased-to ≤50% of control values-following experimental sessions in which acute lorcaserin was administered. CONCLUSIONS: These data indicate that lorcaserin reduces IV self-administration of nicotine at a dose that decreases motoric activity but less consistently disrupts food-maintained responding. Further research into lorcaserin's potential utility for the management of nicotine dependence is warranted.