Comparison of the effects of bupropion and nicotine on locomotor activation and dopamine release in vivo.
Bupropion is an atypical anti-depressant that is approved for smoking cessation. In addition to inhibiting dopamine reuptake, bupropion has been reported to block nicotinic acetylcholine receptors in vitro, and this action might contribute to its efficacy for smoking cessation. In this study we investigated if nicotinic receptor-mediated responses in vivo are decreased in the presence of a behaviorally effective dose of bupropion. In separate experiments we measured locomotor activation and dopamine overflow in the nucleus accumbens core, using in vivo microdialysis in freely moving rats. Bupropion (30 mg/kg i.p.) increased locomotor activity, which remained elevated for up to 2 h. Nicotine (0.4 mg/kg s.c.) also increased locomotor activity but for a shorter duration. When given 20 min after bupropion, hyperlocomotion was significantly enhanced, compared to the response to either nicotine or bupropion alone, consistent with the effects of the two drugs being additive. Systemic administration of bupropion (30 mg/kg i.p.) also elicited a significant increase in dopamine overflow (113+/-16% above basal levels). Nicotine (3 mM; delivered into the nucleus accumbens core via the microdialysis probe) increased dopamine overflow by 126 +/- 35%. Nicotine delivered during the response to bupropion resulted in enhanced dopamine overflow of 294 +/- 50%, also consistent with the actions of the two drugs being additive. This study suggests that behaviorally effective concentrations of bupropion in the rat do not diminish the effects of nicotine by blocking nicotinic receptors.
Department of Biology and Biochemistry, University of Bath, Bath, UK.
Nimish
N
Sidhpura
Peter
P
Redfern
Helen
H
Rowley
David
D
Heal
Susan
S
Wonnacott
D000818:Animals; D016642:Bupropion / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D016642:Bupropion; D009538:Nicotine; D004298:Dopamine