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

Abstract

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 3–4times 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.

Confronting the challenge of failed translation in medications development for substance use disorders

“…Of particular importance, results in SODs with methadone for opioid use disorder and bupropion for smoking cessation have often been inconsistent with the clinical effectiveness of these compounds. Methadone ( Jones and Prada, 1977 ; Mello et al, 1983 ) and bupropion ( Rauhut et al, 2003 ; Shoaib et al, 2003 ; Rauhut et al, 2005 ; de Moura et al, 2020 ) generally decrease rates of drug self-administration only at doses that also produce decrease in responding for other reinforcers along with other evidence for behavioral impairment. This indicates that SODs are vulnerable not only to false-positive effects (i.e.…”

Confronting the challenge of failed translation in medications development for substance use disorders

“…Of particular importance, results in SODs with methadone for opioid use disorder and bupropion for smoking cessation have often been inconsistent with the clinical effectiveness of these compounds. Methadone ( Jones and Prada, 1977 ; Mello et al, 1983 ) and bupropion ( Rauhut et al, 2003 ; Shoaib et al, 2003 ; Rauhut et al, 2005 ; de Moura et al, 2020 ) generally decrease rates of drug self-administration only at doses that also produce decrease in responding for other reinforcers along with other evidence for behavioral impairment. This indicates that SODs are vulnerable not only to false-positive effects (i.e.…”

Confronting the challenge of failed translation in medications development for substance use disorders

“…Of particular importance, results in SODs with methadone for opioid use disorder and bupropion for smoking cessation have often been inconsistent with the clinical effectiveness of these compounds. Methadone ( Jones and Prada, 1977 ; Mello et al, 1983 ) and bupropion ( Rauhut et al, 2003 ; Shoaib et al, 2003 ; Rauhut et al, 2005 ; de Moura et al, 2020 ) generally decrease rates of drug self-administration only at doses that also produce decrease in responding for other reinforcers along with other evidence for behavioral impairment. This indicates that SODs are vulnerable not only to false-positive effects (i.e.…”

Confronting the challenge of failed translation in medications development for substance use disorders

“…Of particular importance, results in SODs with methadone for opioid use disorder and bupropion for smoking cessation have often been inconsistent with the clinical effectiveness of these compounds. Methadone ( Jones and Prada, 1977 ; Mello et al, 1983 ) and bupropion ( Rauhut et al, 2003 ; Shoaib et al, 2003 ; Rauhut et al, 2005 ; de Moura et al, 2020 ) generally decrease rates of drug self-administration only at doses that also produce decrease in responding for other reinforcers along with other evidence for behavioral impairment. This indicates that SODs are vulnerable not only to false-positive effects (i.e.…”