Nicotine-induced Fos expression in the nucleus accumbens and the medial prefrontal cortex of the rat: Role of nicotinic and NMDA receptors in the ventral tegmental area

We have previously shown that the nicotine-induced dopamine release in the nucleus accumbens can be attenuated by local administration into the ventra l tegmental area (VTA), of antagonists at nicotinic and N-methyl-D-aspartat e (NMDA), but not alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMP A) receptors. In the present study, we investigated the role of nicotinic a nd NMDA receptors in the VTA for the expression of Fos-like immunoreactivit y (FLI) in the shell and core of the nucleus accumbens and in the medial pr efrontal cortex (mPFC) of the rat after acute nicotine administration. Syst emically administered nicotine increased FLI in both the mPFC and the nucle us accumbens when compared to saline controls, although this effect was mor e pronounced, and reached statistical significance in the nucleus accumbens , especially in the core region. When mecamylamine was delivered by reverse dialysis into the VTA, the systemic nicotine-induced FLI was significantly attenuated in the nucleus accumbens. Similarly, the NMDA receptor antagoni st 2-amino-5-phosphonopentanoic acid (AP-5), infused locally in the VTA, al so antagonized the nicotine-induced FLI in the nucleus accumbens, Neither m ecamylamine nor AP-5 alone affected basal FLI levels in any of the structur es studied. Local administration of nicotine in the VTA increased FLI in th e nucleus accumbens but not in the mPFC. Since the nicotine-induced FLI is probably due to an increased dopamine release in both the nucleus accumbens and the mPFC, we conclude that FLI in the nucleus accumbens is mediated, t o a large extent, through the activation of dopamine neurons via nicotinic and NMDA receptors in the VTA, whereas the nicotine-induced FLI in the mPFC is subjected to a differential control mechanism, tentatively involving ni cotinic receptors at the terminal level of the mPFC-projecting dopamine neu rons. Synapse 36:314-321, 2000. (C) 2000 Wiley-Liss, Inc.