Induction of Fos-immunostaining by nicotine and nicotinic receptor antagonists in rat brain

Using Fos protein immunohistochemistry, we have studied the effects of acut e nicotine (0.5 mg/kg s.c.) and nicotinic acetylcholine receptor (nAChR) an tagonists in eleven rat brain areas. Acute nicotine elevated Fos-like immun ostaining (Fos IS) significantly in all studied areas except the medial pre frontal cortex. Nicotine increased the Fos IS in cortical, limbic and hypot halamic areas by 2-10-fold, and in the interpeduncular nucleus as well as i n the visual areas the increases were 15-150-fold. When given alone, the nA ChR antagonists mecamylamine (1.0 or 5.0 mg/kg i.p.) and dihydro-beta-eryth roidine (DHE; 1.4 or 2.8 mg/kg i.p,) increased Fos IS in most brain areas m aximally by 2-10-fold, but methyllycaconitine (MLA; 4.0 mg/kg i.p.) only in three areas and maximally by 4-fold. The efficacy of nAChR antagonists in blocking nicotine's effects on Fos IS varied noticeably with respect to reg ion and antagonist, and the combined effect of nicotine+antagonist did not exceed that of either treatment alone. Mecamylamine and DHE significantly r educed nicotine- induced Fos IS in most of the studied areas, and MLA only in two areas. Thus, nAChRs seem to mediate the effects of nicotine on Fos I S, and the differences in the effects of the antagonists studied suggest th at more than one subtype of nAChRs are involved. The present experiments al so provide evidence that nAChR blockade itself may result in increased Fos protein expression in the brain. This could be due to blockade of presynapt ic nAChRs modulating transmitter release or interruption of complex polysyn aptic feedback pathways. (C) 2001 Elsevier Science Ltd. All rights reserved .