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

• Published in: European journal of pharmacology 2007-01, Vol.554 (2), p.128-136
• Main Authors: Middleton, Lisa S., Apparsundaram, Subbu, King-Pospisil, Kelley A., Dwoskin, Linda P.
• Format: Article
• Language: English
• Subjects: Animals; Binding, Competitive - drug effects; Biological and medical sciences; Biological Transport - physiology; Blotting, Western - methods; Cell Membrane - drug effects; Cell Membrane - metabolism; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine - pharmacokinetics; Dopamine Plasma Membrane Transport Proteins - analysis; Dopamine Plasma Membrane Transport Proteins - physiology; Dopamine transporter; Ganglionic Stimulants - administration & dosage; Ganglionic Stimulants - pharmacology; Injections, Subcutaneous; Kinetics; Male; Medical sciences; Nicotine; Nicotine - administration & dosage; Nicotine - pharmacology; Pharmacology. Drug treatments; Piperazines - metabolism; Rats; Rats, Sprague-Dawley; Synaptosomes - drug effects; Synaptosomes - metabolism; Time Factors; Trafficking; Tritium
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.09.074

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 V max of [ 3H]dopamine uptake at 10 and 40 min. To determine whether the increase in V max 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.