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

Abstract

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.

Nicotinic Receptor Activation Increases [3H]Dopamine Uptake and Cell Surface Expression of Dopamine Transporters in Rat Prefrontal Cortex

“…1) or K m (PFC: nicotine, 23.1 Ϯ 2.7 nM and saline, 21.0 Ϯ 1.9 nM; striatum: nicotine, 28.2 Ϯ 3.9 nM and saline, 26.0 Ϯ 4.5 nM). The current results from striatum with the low dose of nicotine are different from those reported previously (Middleton et al, 2007), in which nicotine (0.32 mg/kg s.c.) produced a small increase (23%) in V max in striatum (for explanation of the discrepancy in the results, see Discussion). In the current study, a higher dose of nicotine (0.8 mg/kg) also did not alter V max (Fig.…”

“…We reported recently that nicotine (0.3 mg/kg) produced a small, but significant, 23% increase in V max in rat striatum at 10 and 40 min after injection, which was not accompanied by an increase in cell surface DAT expression (Middleton et al, 2007). In the current study, no significant effect of this nicotine dose was observed during the 60-min period after injection; however, there was a tendency for a nicotine-induced increase (ϳ20%) in V max in striatum (Fig.…”

Nicotine and amphetamine acutely cross-potentiate their behavioral and neurochemical responses in female Holtzman rats

“…Nicotine increased dopamine clearance in the striatum (Hart and Ksir 1996;Middleton et al 2004Middleton et al , 2007a, and Middleton et al (2007a) further reported that nicotine increased the V max of rat striatal dopamine uptake in a manner independent of transporter trafficking. This effect on transporter function was transient in that it lasted less than 1 h. It is difficult to reconcile this finding with the present data because decreased synaptic dopamine would not be expected to exaggerate amphetamine response, unless it made more dopamine available for amphetamine-stimulated release or assisted the transport of amphetamine into the terminal.…”

Involvement of Neurotransmitter and Nrf2 in Nicotine- and Cigarette Smoke-Induced Testicular Toxicity in Adult Rats

“…Another issue relevant to this study is nicotine-, nornicotine-(produced by nicotine), and nicotine's metabolic intermediate, cotinineinduced release of DA through activation of nACh Rs. 50 We also explored a remarkable dose-and time-dependent shift of serum cotinine level in the experimental animals toward higher side without any detection in the controls as a result of the applied doses that resemble the human smoking scenario. 39 Serum cotinine is not detected in the control animals due to the nonavailability of the substance in the serum throughout the study period, suggesting toxic impact of the studied doses upon exposure, which corroborates several previous observations.…”