Nicotine-induced behavioral sensitization is associated with extracellulardopamine release and expression of c-Fos in the striatum and nucleus accumbens of the rat

It is well known that repeated injections of nicotine produce progressively larger increases in locomotor activity, an effect referred to as behaviora l sensitization. This study was carried out to investigate the neural mecha nisms underlying nicotine-induced behavioral sensitization using in vivo mi crodialysis and Fos-like immunohistochemistry (FLI). Rats were given repeat ed injections of saline or nicotine (0.4 mg/kg s.c., twice daily for 7 days ) followed by one challenge injection on the 4th day after the last daily i njection. Systemic challenge with nicotine produced a much larger increase in locomotor activity in nicotine-pretreated rats (659.1 +/- 94.9 counts/2 h) than in saline-pretreated rats (218.1 +/- 61 counts/2 h). A direct focal challenge of nicotine (1 or 5 mM) via a microdialysis probe in the nucleus accumbens or striatum induced a much greater dose-dependent increase of do pamine (DA) output in nicotine-pretreated rats than in saline-pretreated ra ts. Furthermore, in parallel with the behavioral and biochemical data, syst emic challenge with nicotine produced marked Fos-like immunohistochemistry in the nucleus accumbens and the striatum in the nicotine-pretreated rats. Taken together, this study demonstrates that behavioral sensitization is cl early associated with an increase in DA release and activation of Fos-like immunoreactive cells in the striatum and the nucleus accumbens produced by repeated nicotine treatment. Our results strongly suggest that the striatum and the nucleus accumbens may play a major role in nicotine-induced behavi oral sensitization. The present results are discussed in terms of the devel opment and expression of nicotine-induced behavioral sensitization. (C) 200 1 Elsevier Science B.V. All rights reserved.