Effect of bupropion on nicotine self-administration in rats

Abstract

These results suggest that high bupropion doses decrease responding nonspecifically; whereas low bupropion doses selectively increase responding for nicotine. The increase in nicotine self-administration is likely due to inhibition of dopamine and norepinephrine transporters, combined with inhibition of nAChRs.

Methylphenidate Enhances the Abuse-Related Behavioral Effects of Nicotine in Rats: Intravenous Self-Administration, Drug Discrimination, and Locomotor Cross-Sensitization

“…However, since there were no differences in the effect of pretreatment with 10 mg/kg of methylphenidate between rats self-administering either nicotine unit dose, it is possible that high doses of stimulants can alter nicotine self-administration nonspecifically. While the precise reason(s) for this biphasic pattern of results is unknown, Rauhut et al (2003) found similar biphasic dose effects of acute bupropion or methamphetamine pretreatment on nicotine self-administration in rats. Prada and Goldberg (1985) also reported that caffeine pretreatment increased nicotine self-administration in squirrel monkeys at low doses (3-10 mg/kg), while higher doses (60-100 mg/kg) decreased response rates.…”

“…As these mechanisms would suggest, it has been shown that coadministration of methylphenidate augments nicotineinduced increases in extracellular dopamine content in the NAcc (Gerasimov et al, 2000a, b), suggesting that the interactive effects of these drugs on mesolimbic dopamine transmission underlies the behavioral interactions noted in the present study. Regarding self-administration specifically, blockade of central dopamine receptors reduces nicotine self-administration (Corrigall and Coen, 1991;Corrigall et al, 1992), whereas administration of monoamine oxidase inhibitors or the dopamine reuptake inhibitor bupropion increases nicotine self-administration (Guillem et al, 2005(Guillem et al, , 2006Rauhut et al, 2003). One caveat to this interpretation is that methylphenidate and bupropion are relatively nonselective inhibitors of the norepinephrine and dopamine transporters Han and Gu, 2006).…”

“…In a microdialysis study using rats, coadministration of cocaine with nicotine was shown to produce an additive increase in extracellular dopamine levels in the nucleus accumbens (NAcc) relative to administration of nicotine alone (Gerasimov et al, 2000a, b). Similarly, behavioral studies have shown that administration of indirect dopamine agonists, such as monoamine oxidase inhibitors (which prevent intracellular metabolism of dopamine) or bupropion (a dopamine reuptake inhibitor), increase nicotine self-administration in rats (Guillem et al, 2005(Guillem et al, , 2006Rauhut et al, 2003). Thus, it is possible that stimulant drugs increase nicotine self-administration, at least in part, by augmenting nicotine-induced increases in extracellular dopamine levels in the NAcc.…”

Nicotine and methamphetamine share discriminative stimulus effects

“…Nicotine attenuated reinstatement of methamphetamine self-administration (Hiranita et al, 2004;Hiranita et al, 2006), and mecamylamine decreased methamphetamine self-administration in rats (Glick et al, 2002). In rats trained to self-administer nicotine, bupropion and methamphetamine increased selfadministration of low doses of nicotine and decreased self-administration of high doses of nicotine (Rauhut et al, 2003). These findings indicate a definite interaction between the two compounds; in particular, that the two compounds produce cross-sensitization implies a similar mechanism.…”

“…The most obvious possibility is that nicotinic acetylcholine receptors are located on dopaminergic neurons in the ventral tegmental area which are important in regulating neuronal activity of these dopaminergic neurons (Mameli-Engvall et al, 2006;Ungless and Cragg, 2006). Administration of nicotine modulates dopamine release (Quarta et al, 2006;Wonnacott et al, 2005), and is known to alter behaviors controlled by these dopaminergic pathways including locomotor behavior (Kuribara, 1999;Suemaru et al, 1993) and self-administration of abused compounds, including both nicotine and methamphetamine (Glick et al, 2002;Hiranita et al, 2004;Hiranita et al, 2006;Rauhut et al, 2003). The failure of mecamylamine to block the cross-substitution of methamphetamine in nicotine-trained rats may be related to the finding that perfusion of mecamylamine into the nucleus accumbens did not alter dopamine levels in the ventral tegmental area or the nucleus accumbens (Rahman and McBride, 2002).…”