Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation
Article first published online: 4 DEC 2006
Copyright © 2006 Wiley-Liss, Inc.
Volume 61, Issue 3, pages 157–165, March 2007
How to Cite
Middleton, L. S., Crooks, P. A., Wedlund, P. J., Cass, W. A. and Dwoskin, L. P. (2007), Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation. Synapse, 61: 157–165. doi: 10.1002/syn.20351
- Issue published online: 4 DEC 2006
- Article first published online: 4 DEC 2006
- Manuscript Accepted: 5 OCT 2006
- Manuscript Received: 6 SEP 2006
- NIH. Grant Numbers: U19 DA 017548, DA 00399, DA 15292
- DA transporter;
- nicotinic receptors;
- in vivo voltammetry
Nornicotine, a tobacco alkaloid and N-demethylated nicotine metabolite, releases DA from superfused rat striatal slices in a mecamylamine-sensitive manner, indicating nicotinic receptor (nAChR) modulation of this response. The current study determined the effect of nornicotine on rat striatal dopamine transporter (DAT) function using in vivo voltammetry. In a dose-related and mecamylamine-sensitive manner, nornicotine (0.35–12.0 mg/kg, s.c.) decreased DA clearance, suggesting that nornicotine inhibits striatal DAT function via a nAChR–mediated mechanism. Furthermore, the nAChRs mediating the nornicotine-induced inhibition of DAT function appear to be different from those activated by nicotine which increases DA clearance. Understanding the actions of nornicotine in brain may have significance for emerging therapeutics and for the management of nicotine dependence. Synapse 61:157–165, 2007. © 2006 Wiley-Liss, Inc.