Role of astrocytes in nicotine-induced motor excitement symptoms

Abstract

Nicotine elicits motor excitement symptoms such as tremor and convulsive seizures. We performed behavioral studies in combination with the brain mapping analysis of glial fibrillary acidic protein (GFAP), a marker of astrocytic activation, to clarify the role of astrocytes in nicotine-induced tremor and convulsive seizures. Intraperitoneal (i.p.) injection of nicotine induced straub tail and tremor at 0.3 or 1 mg/kg, and convulsive seizures at 3 mg/kg in mice. Immunohistochemical examination revealed that nicotine region-specifically elevated GFAP expression in the piriform cortex (PirC) at 1 mg/kg (i.p.), and CA3 area and dentate gyrus (DG) of hippocampus at 0.3-3 mg/kg (i.p.). We next evaluated the effect of fluorocitrate (FC), an astrocyte inhibitor, on nicotine-induced tremor and convulsive seizures. Intracerebroventricular injection of FC (1 nmol) reduced GFAP expression in PirC, basolateral amygdala, CA2, CA3 and DG. Whereas FC did not affect the generation of nicotine tremor, it caused a significant decrease in seizure intensity and a decreased incidence of seizures. These results suggest that astrocytic activation by nicotine in PirC, CA3 or DG is involved in nicotine-induced convulsive seizures.