Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation

Lisa S. Middleton; Peter A. Crooks; Peter J. Wedlund; Wayne A. Cass; Linda P. Dwoskin

doi:10.1002/syn.20351

Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation

Lisa S. Middleton, Peter A. Crooks, Peter J. Wedlund, Wayne A. Cass, Linda P. Dwoskin

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	157-165
Number of pages	9
Journal	Synapse
Volume	61
Issue number	3
DOIs	https://doi.org/10.1002/syn.20351
State	Published - Mar 2007

Keywords

DA transporter
In vivo voltammetry
Nicotine
Nicotinic receptors
Nornicotine

ASJC Scopus subject areas

Cellular and Molecular Neuroscience

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10.1002/syn.20351

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title = "Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation",

abstract = "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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AU - Middleton, Lisa S.

AU - Crooks, Peter A.

AU - Wedlund, Peter J.

AU - Cass, Wayne A.

AU - Dwoskin, Linda P.

PY - 2007/3

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N2 - 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.

AB - 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.

KW - DA transporter

KW - In vivo voltammetry

KW - Nicotine

KW - Nicotinic receptors

KW - Nornicotine

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Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation

Abstract

Keywords

ASJC Scopus subject areas

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