Nicotine increases dopamine transporter function in rat striatum through a trafficking-independent mechanism

Lisa S. Middleton, Subbu Apparsundaram, Kelley A. King-Pospisil, Linda P. Dwoskin

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


In previous in vivo voltammetry studies, acute nicotine administration increased striatal dopamine clearance. The current study aimed to determine whether nicotine also increases [3H]dopamine uptake across the time course of the previous voltammetry studies and whether dopamine transporter trafficking to the cell surface mediates the nicotine-induced augmentation of dopamine clearance in striatum. Rats were administered nicotine (0.32 mg/kg, s.c.); striatal synaptosomes were obtained 5, 10, 40 or 60 min later. Nicotine increased (25%) the Vmax of [3H]dopamine uptake at 10 and 40 min. To determine whether the increase in Vmax was due to an increase in dopamine transporter density, [3H]GBR 12935 (1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine dihydrochloride) binding was performed using rat striatal membranes; no differences were found between nicotine and saline-control groups at 5, 10 or 40 min post-injection, indicating that nicotine did not increase striatal dopamine transporter density; however, [3H]GBR 12935 binding assays determine both cell surface and intracellular dopamine transporter. Changes in cellular dopamine transporter localization in striatum were determined using biotinylation and subfractionation approaches; no differences between nicotine and saline-control groups were observed at 10 and 40 min post-injection. These results suggest that the nicotine-induced increase in dopamine uptake and clearance in striatum may occur via a trafficking-independent mechanism.

Original languageEnglish
Pages (from-to)128-136
Number of pages9
JournalEuropean Journal of Pharmacology
Issue number2-3
StatePublished - Jan 12 2007

Bibliographical note

Funding Information:
The authors would like to thank Agripina G. Deaciuc and Jackie Huller for their expert technical assistance, and Kathleen Grzech for editing the manuscript. This work was supported by National Institute of Health grants F31DA15292 (LM), R21DA018372 (LD, SA), KO2DA00399 (LD) and a grant from NARSAD (SA).


  • Dopamine transporter
  • Nicotine
  • Trafficking

ASJC Scopus subject areas

  • Pharmacology


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