Comparison of the effects of bupropion on nicotinic receptor-evoked [(3) H]dopamine release from rat striatal synaptosomes and slices

N Sidhpura, P Reffern, S Wonnacott

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Tobacco smoking is a nicotine addiction, mediated in part by the ability of nicotine to elicit dopamine release, as a result of the stimulation of nicotinic acetylcholine receptors associated with dopaminergic pathways. The smoking cessation agent bupropion is an inhibitor of the dopamine transporter, but has also been shown to inhibit nicotinic acetylcholine receptors. To assess the relative impact of its actions at these two targets, we have examined the effects of bupropion on nicotine-evoked [H-3]dopamine release from rat striatal synaptosomes and slices, in the absence of any other transporter inhibitor. Bupropion (10 mu M) significantly decreased nicotine-evoked [H-3]dopamine release by similar to 50% in both preparations, consistent with the blockade of nicotinic receptors. In support of this interpretation, bupropion also selectively inhibited nicotine-evoked Ca2+ increases in SH-SY5Y cells. In striatal slices (but not in synaptosomes) the concentration-response profile for bupropion has an inverted 'u' shape, with a decrease in nicotine-evoked [H-3]dopamine release also observed in the presence of 0.1 mu M bupropion. This effect of 0.1 mu M bupropion (but not 10 mu M bupropion) was reversed by the dopamine D-2, receptor antagonist raclopride. We propose that modest blockade of the dopamine transporter by low concentrations of bupropion results in feedback inhibition via dopamine D-2 autoreceptors. This is overcome at higher concentrations of bupropion, before inhibition of nicotinic receptors occurs. Therefore bupropion's inhibition of the dopamine transporter and nicotinic receptors appears to be separated with respect to concentration.
Original languageEnglish
Pages (from-to)102-109
Number of pages8
JournalEuropean Journal of Pharmacology
Volume567
Issue number1-2
DOIs
Publication statusPublished - Jul 2007

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