Chronic nicotine enhances basal and nicotine-induced Fos immunoreactivity preferentially in the medial prefrontal cortex of the rat.

In the present study, expression of the immediate early gene protein products Fos and Jun-B within the dorsolateral striatum, the core and shell of the nucleus accumbens (NAC), the medial prefrontal cortex (mPFC), and the ventrolateral orbital cortex was examined. Rats were injected s.c. with either saline or nicotine (0.5 mg/kg) once daily for 12 days. On day 13, animals received a challenge injection of either saline or nicotine (0.5 or 1.0 mg/kg, s.c.) and 2 h later their brains were examined for Fos-like (FLI) and Jun-B-like (JLI) immunoreactivity. Chronic nicotine significantly increased basal expression of FLI selectively in the mPFC. Nicotine challenge significantly increased FLI in the mPFC of saline-treated animals and even further increased FLI in the mPFC of nicotine-treated animals. In the shell of the NAC, nicotine challenge also increased FLI in nicotine-treated animals, whereas it increased JLI only in saline-treated animals. After chronic nicotine treatment, injection of D1 receptor antagonist SCH 23390 (0.1 mg/kg, i.p.) 10 min before a nicotine challenge (0.5 mg/kg, s.c.), significantly attenuated the nicotine-induced FLI in the mPFC and the shell of the NAC. These results suggest that the regionally selective effect of nicotine challenge on FLI is due to enhanced dopaminergic transmission, mediated via stimulation of D1 receptors.