Nicotine Effects on Dopamine Clearance in Rat Nucleus Accumbens

Abstract

In vivo voltammetry was used to measure the clearance of exogenously applied dopamine (DA) in the nucleus accumbens following acute systemic nicotine administration in urethane‐anesthetized rats. The IVEC‐5 system was used for continuous in vivo electrochemical measurements. A finite amount of DA was pressure‐ejected (25–100 nl, 200 µM barrel concentration) at 5‐min intervals from micropipettes (tip diameter, 10–15 µm) positioned 250 ± 50 µm from the recording electrode. The peak DA concentration after each DA ejection was significantly decreased in rats following nicotine, but not in rats given saline. In addition, when mecamylamine was administered 20 min before nicotine it clearly antagonized nicotine effects. These results suggest that nicotine may actually facilitate DA transporter systems within the nucleus accumbens.

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

“…The current results support and extend previous findings, showing that systemically administered nicotine increases DA clearance in several dopaminergic terminal regions, including mPFC and striatum (current study) and nucleus accumbens (Hart and Ksir, 1996). The latter results are surprising since stimulation of nAChRs results in depolarization of the plasma membrane (Calabresi et al, 1989), and depolarization of the membrane generally decreases DA transport velocity (Sonders et al, 1997).…”

“…The dose of mecamylamine chosen was also within the range of that inhibiting nicotine self-administration in rats (Rauhut et al, 2002;Rezvani et al, 2002). Mecamylamine (1.0 mg/kg) also was shown to inhibit the effect of nicotine to enhance DA clearance in nucleus accumbens using in vivo voltammetry (Hart and Ksir, 1996). Based on the results of the current nicotine dose-response curves in the first series of experiments, nicotine doses (0.8 and 0.4 mg/kg) that produced a maximal effect in striatum and mPFC, respectively, were chosen.…”

“…One-way ANOVAs were also conducted on the dose response for signal amplitude and clearance rate data from mPFC at each time point during the 30 -60 min period following nicotine injection. The time period chosen for the latter analyses was based on previous results in rat nucleus (Hart and Ksir, 1996). Dunnett's post hoc analysis was performed to determine differences from control.…”

“…The observation that nicotine enhances DAT function in nucleus accumbens in vivo (Hart and Ksir, 1996) is not expected considering the electrogenic nature of the transporter. Translocation of DA by DAT across the membrane is coupled with the cotransport of two Na ϩ ions and one Cl -ion down their electrochemical gradients, generating a small inward current (Kanner and Schuldiner, 1987;Rudnick and Clark, 1993).…”

“…The antidepressant and tobacco use cessation agent, bupropion, inhibits DAT function, but also is a nAChR antagonist (Hurt et al, 1997;Slemmer et al, 2000;Miller et al, 2002). Surprisingly, nicotine (0.4 mg/kg) has been reported to increase DA clearance (enhance DAT function) in the nucleus accumbens in anesthetized rats (Hart and Ksir, 1996). The latter results also contrast findings in vitro in which nicotine and another nicotinic agonist, 1,1-dimethyl-4-phenyl-piperazinium, have been reported to decrease [ 3 H]DA uptake into chopped striatum and PC12 cells, respectively (Izenwasser et al, 1991;Huang et al, 1999).…”