Bupropion Inhibits Nicotine-Evoked [³H]Overflow from Rat Striatal Slices Preloaded with [³H]Dopamine and from Rat Hippocampal Slices Preloaded with [³H]Norepinephrine

Abstract

Bupropion, an efficacious antidepressant and smoking cessation agent, inhibits dopamine and norepinephrine transporters (DAT and NET, respectively). Recently, bupropion has been reported to noncompetitively inhibit ␣3␤2, ␣3␤4, and ␣4␤2 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes or established cell lines. The present study evaluated bupropion-induced inhibition of native ‫ء2␤3␣‬ and ‫ء4␤3␣‬ nAChRs using functional neurotransmitter release assays, nicotine-evoked 3 H]NE overflow. Thus, bupropion acts as an antagonist at ‫ء2␤3␣‬ and ‫ء4␤3␣‬ nAChRs in rat striatum and hippocampus, respectively, across the same concentration range that inhibits DAT and NET function. The combination of nAChR and transporter inhibition produced by bupropion may contribute to its clinical efficacy as a smoking cessation agent.

Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat

“…Moreover, recent evidence suggests that bupropion may act as a functional antagonist at neuronal nicotinic acetylcholine receptors (Fryer and Lukas 2002;Slemmer et al 2000;Miller et al 2002). Our data showing blockade of the acute rewarding effects of nicotine by bupropion at a dose that was ineffective on its own supports this hypothesis.…”

Effect of bupropion on nicotine self-administration in rats

“…Amelioration of withdrawal symptoms associated with smoking cessation may be responsible for the decrease in smoking behavior (Jorenby et al 1999;Shiffman et al 2000). While the pharmacological mechanism by which bupropion effectively reduces smoking has not been elucidated, this antidepressant has been reported to be a nicotinic receptor antagonist in recombinant receptor expression assays (Fryer and Lucas 1999;Slemmer et al 2000) and in native receptor assays (Miller et al 2002). Additionally, bupropion is a non-selective inhibitor of DAT and NET (see above).…”

Effects of bupropion on simulated demand for cigarettes and the subjective effects of smoking

“…In addition, Miller, Sumithran, and Dwoskin (2002) and others (Fryer & Lukas, 1999;Slemmer, Martin, & Damaj, 2000) have demonstrated that bupropion acts as an antagonist on several nicotinic acetylcholine receptors. This latter effect suggests that bupropion may attenuate the reinforcing properties of nicotine (Paterson, 2009).…”