Nicotine modulates restraint‐induced anxiety‐like behavior and c‐Fos expression in mice

Abstract

Nicotine is the main component of tobacco. Clinical evidence suggests that nicotine reduces anxiety in stressful situations. However, in rodents, nicotine can be anxiolytic, anxiogenic, or have no effect on anxiety, depending on the dose and the route of administration, even when the same behavioral test is performed. In the present study, we investigated the effect of nicotine on restraint-induced anxiety-like behavior and c-Fos expression, an index of neuronal activation in the brain. NMRI male mice were individually restricted in round plastic containers (3 cm in diameter, 12 cm in length). Restraint stress induced anxiety-like behavior in the elevated plus-maze and nicotine (0.25mg/kg, i.p.) attenuated the stress-induced changes. The effect of nicotine on stress-induced the anxiolytic was blocked by a nonselective nicotinic receptor antagonist, mecamylamine, but not methalllycaconitine, a selectiveá7 nicotinic receptor antagonist. In addition, restraint stress led to a significant increase of c-Fos expression in several brain regions, including paraventricular hypothalamic nucleus (PVN), lateral hypothalamic area (LH), central amygdaloid nucleus (CeA), basolateral amygdaloid nucleus (BLA), paraventricular thalamic nucleus (PVT), cingulate and retrosplenial cortices (Cg/Rs). Nicotine attenuated the restraint-induced expression of c-Fos in the PVN, LH, CeA and Cg/Rs, while leaving the BLA, PVT unaffected. These results suggest that nicotine may modify the stress-induced behavioral change via regulating the neuronal activation in selected brain regions. (NHRI-93-9112NC)