Induction of Fos-immunostaining by nicotine and nicotinic receptor antagonists in rat brain.
Using Fos protein immunohistochemistry, we have studied the effects of acute nicotine (0.5 mg/kg s.c.) and nicotinic acetylcholine receptor (nAChR) antagonists in eleven rat brain areas. Acute nicotine elevated Fos-like immunostaining (Fos IS) significantly in all studied areas except the medial prefrontal cortex. Nicotine increased the Fos IS in cortical, limbic and hypothalamic areas by 2-10-fold, and in the interpeduncular nucleus as well as in the visual areas the increases were 15-150-fold. When given alone, the nAChR antagonists mecamylamine (1.0 or 5.0 mg/kg i.p.) and dihydro-beta-erythroidine (DHE; 1.4 or 2.8 mg/kg i.p.) increased Fos IS in most brain areas maximally 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 region and antagonist, and the combined effect of nicotine+antagonist did not exceed that of either treatment alone. Mecamylamine and DHE significantly reduced 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 IS, and the differences in the effects of the antagonists studied suggest that more than one subtype of nAChRs are involved. The present experiments also provide evidence that nAChR blockade itself may result in increased Fos protein expression in the brain. This could be due to blockade of presynaptic nAChRs modulating transmitter release or interruption of complex polysynaptic feedback pathways.
Seppä
T
T
Division of Pharmacology and Toxicology, Department of Pharmacy, University of Helsinki, P.O. Box 56, Viikinkaari 5, FIN-00014 Helsinki, Finland. liisa.ahtee@helsinki.fi
Salminen
O
O
Moed
M
M
Ahtee
L
L
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects*
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011978:Receptors, Nicotinic; D009538:Nicotine