Journal
SYNAPSE
Volume 61, Issue 3, Pages 157-165Publisher
WILEY
DOI: 10.1002/syn.20351
Keywords
DA transporter; nicotine; nicotinic receptors; nornicotine; in vivo voltammetry
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Funding
- NIDA NIH HHS [DA 00399, DA 15292, U19 DA 017548] Funding Source: Medline
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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.
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