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Middleton LS, Apparsundaram S, King-Pospisil KA, Dwoskin LP: Nicotine increases dopamine transporter function in rat striatum through a trafficking-independent mechanism. Eur J Pharmacol. 2007 Jan 12;554(2-3):128-36. Epub 2006 Oct 19.
In previous in vivo voltammetry studies, acute nicotine administration increased striatal dopamine clearance. The current study aimed to determine whether nicotine also increases [(3) H] 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 V (max) of [(3) H] dopamine uptake at 10 and 40 min. To determine whether the increase in V (max) was due to an increase in dopamine transporter density, [(3) H] 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, [(3) H] 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. |
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