The effects of nicotine on nitric oxide induced anxiogenic-like behaviors in the dorsal hippocampus

Abstract

Nicotine, an active tobacco derived alkaloid, regulates the activity of the neuronal nitric oxide synthase (nNOS) as well as the release of nitric oxide (NO) in the nervous system. Nicotinic acetylcholine receptors and nNOS are abundantly co-expressed in the hippocampal neurons and are found to alter anxiety-like behaviors in rodents. Dorsal hippocampus may be a site for modulation of anxiety. Therefore, in this study, we investigated the possible interactions between nicotine and NO systems of the dorsal hippocampus and the resultant effect on anxiety-like behaviors. The elevated plus-maze (EPM) test has been used to test the anxiety. Intraperitoneal administration of nicotine (0.5mg/kg) decreased the open arm time percentage (%OAT) and open arm entries percentage (%OAE) but not the locomotor activity, indicating an anxiogenic-like response. Intra-CA1 injection of l-arginine (a NO precursor) or l-NAME (a NOS inhibitor) also caused anxiogenic-like effects. On the other hand, injection of the low dose nicotine before different doses of l-arginine or l-NAME blocked the anxiogenic-like response induced by the drugs. Our results suggested that, both NO and nicotinic cholinergic systems not only play a part in the modulation of the anxiety in mice dorsal hippocampus, but also demonstrate a complex interaction in this respect.