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.
Authors	Lisa S Middleton, Peter A Crooks, Peter J Wedlund, Wayne A Cass, Linda P Dwoskin
Journal	Synapse (New York, N.Y.) (Synapse) Vol. 61 Issue 3 Pg. 157-65 (Mar 2007) ISSN: 0887-4476 [Print] United States
PMID	17146768 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Dopamine Plasma Membrane Transport Proteins Insecticides Nicotinic Agonists Nicotinic Antagonists Receptors, Nicotinic Mecamylamine Nicotine nornicotine Acetylcholine Dopamine
Topics	Acetylcholine (metabolism) Animals Corpus Striatum (drug effects, metabolism, physiopathology) Dopamine (metabolism) Dopamine Plasma Membrane Transport Proteins (antagonists & inhibitors, metabolism) Dose-Response Relationship, Drug Drug Interactions (physiology) Insecticides (pharmacology) Male Mecamylamine (pharmacology) Metabolic Clearance Rate (drug effects, physiology) Nicotine (analogs & derivatives, pharmacology) Nicotinic Agonists (pharmacology) Nicotinic Antagonists (pharmacology) Rats Rats, Sprague-Dawley Receptors, Nicotinic (drug effects, metabolism) Synaptic Transmission (drug effects, physiology) Time Factors Tobacco Use Disorder (metabolism, physiopathology)

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