QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.055335v1 308/1/367    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Middleton, L. S. Articles by Dwoskin, L. P. Search for Related Content PubMed PubMed Citation Articles by Middleton, L. S. Articles by Dwoskin, L. P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB DOPAMINE NICOTINE NICOTINE TARTRATE

NEUROPHARMACOLOGY

Nicotinic Receptor Modulation of Dopamine Transporter Function in Rat Striatum and Medial Prefrontal Cortex

College of Pharmacy (L.S.M., L.P.D.) and the Department of Anatomy and Neurobiology (W.A.C.), College of Medicine, University of Kentucky, Lexington, Kentucky

Nicotine activates nicotinic acetylcholine receptors (nAChRs) on dopamine (DA) terminals to evoke DA release, which subsequently is taken back up into the terminal via the DA transporter (DAT). nAChRs may modulate DAT function thereby contributing to the regulation of synaptic DA concentrations. The present study determined the dose-response for nicotine (0.1-0.8 mg/kg, s.c.) to modulate DA clearance in striatum and medial prefrontal cortex (mPFC) using in vivo voltammetry in urethane anesthetized rats and determined if this effect was mediated by nAChRs. Exogenous DA (200 µM) was pressure-ejected at 5-min intervals until reproducible baseline signals were obtained. Subsequently, nicotine or saline was administered, and DA pressure ejection continued at 5-min intervals for 60 min. In both striatum and mPFC, signal amplitude decreased by 20% across the 60-min session in saline-injected rats. A monophasic dose-response curve was found in striatum, with a maximal 50% decrease in signal amplitude after 0.8 mg/kg. In contrast, a U-shaped dose-response curve was found in mPFC, with a maximal 50% decrease in signal amplitude after 0.4 mg/kg. Onset of nicotine response occurred 10 to 15 min after injection in both brain regions; however, the amount of time before maximal response was 45 and 30 min in striatum and mPFC, respectively. Mecamylamine (1.5 mg/kg) completely inhibited the nicotine-induced (0.8 and 0.4 mg/kg) decrease in signal amplitude in striatum and mPFC, respectively, indicating mediation by nAChRs. Thus, nicotine enhances DA clearance in striatum and mPFC in a mecamylamine-sensitive manner, indicating that nAChRs modulate DAT function in these brain regions.

Address correspondence to: Dr. Linda P. Dwoskin, College of Pharmacy, University of Kentucky, Rose Street, Lexington, KY 40536. E-mail: ldwoskin{at}uky.edu

This article has been cited by other articles:

				C. L. Parish, J. Nunan, D. I. Finkelstein, F. N. McNamara, J. Y. Wong, J. L. Waddington, R. M. Brown, A. J. Lawrence, M. K. Horne, and J. Drago Mice Lacking the {alpha}4 Nicotinic Receptor Subunit Fail to Modulate Dopaminergic Neuronal Arbors and Possess Impaired Dopamine Transporter Function Mol. Pharmacol., November 1, 2005; 68(5): 1376 - 1386. [Abstract] [Full Text] [PDF]