Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation
- 4 December 2006
- Vol. 61 (3) , 157-165
- https://doi.org/10.1002/syn.20351
Abstract
Nornicotine, a tobacco alkaloid andN‐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.Keywords
This publication has 35 references indexed in Scilit:
- NICOTINE 5′-OXIDATION AND METHYL OXIDATION BY P450 2A ENZYMESDrug Metabolism and Disposition, 2005
- The Effects of Subunit Composition on the Inhibition of Nicotinic Receptors by the Amphipathic Blocker 2,2,6,6-Tetramethylpiperidin-4-yl HeptanoateMolecular Pharmacology, 2005
- Effect of Dextrometorphan and Dextrorphan on Nicotine and Neuronal Nicotinic Receptors: In Vitro and in Vivo SelectivityThe Journal of Pharmacology and Experimental Therapeutics, 2005
- Nicotinic Receptor Modulation of Dopamine Transporter Function in Rat Striatum and Medial Prefrontal CortexThe Journal of Pharmacology and Experimental Therapeutics, 2004
- Reward mechanisms in the brain and their role in dependence: evidence from neurophysiological and neuroimaging studiesBrain Research Reviews, 2001
- QUANTITATIVE PREDICTION OF IN VIVO DRUG CLEARANCE AND DRUG INTERACTIONS FROM IN VITRO DATA ON METABOLISM, TOGETHER WITH BINDING AND TRANSPORTAnnual Review of Pharmacology and Toxicology, 1998
- Differential Inhibition by α‐Conotoxin‐MII of the Nicotinic Stimulation of [3H]Dopamine Release from Rat Striatal Synaptosomes and SlicesJournal of Neurochemistry, 1998
- Nicotine Effects on Dopamine Clearance in Rat Nucleus AccumbensJournal of Neurochemistry, 1996
- S(‐)‐Nornicotine Increases Dopamine Release in a Calcium‐Dependent Manner from Superfused Rat Striatal SlicesJournal of Neurochemistry, 1993
- High affinity binding of [3H] (−)-nicotine to rat brain membranes and its inhibition by analogues of nicotineNeuropharmacology, 1988