Nicotine modulates nitric oxide in rat brain

Nicotine exerts its central actions by regulating cationic fluxes through n icotinic acetylcholine receptors (nAChRs). By this effect, the drug likely also modifies events occurring beyond the nAChR, including the regulation o f nitric oxide (NO) synthesis. The present study was undertaken to assess t he effects of acute and chronic nicotine administration (0.4 mg/kg, s.c.) o n levels of NO2- + NO3- stable metabolites of NO, in brain regions of male and female rats. Nicotine increased levels of the metabolites, and therefor e presumably of NO, with sex differences in the degree of stimulation, the brain regions affected, and the variance between the effects of acute and c hronic administration. Prior inhibition of NO synthase eliminated the effec t of nicotine in all regions studied. While nicotine appeared to increase N O indirectly via glutamate receptors in the cortex and hippocampus, this wa s not true of the corpus striatum, where blocking NMDA-type glutamate recep tors with MK-801 had no effect. The findings support the view that NO is li kely involved in some of the central effects of nicotine. (C) 2000 Elsevier Science BN. All rights reserved.