Long-term effects of high doses of nicotine on feeding behavior and brain nitric oxide synthase activity in female mice.

We studied the long-term effects of repeated doses of nicotine, causing dependence, 120 days after its withdrawal on feeding behavior and on brain nitric oxide (NO) formation in female mice. Nicotine dependence was induced by subcutaneous (s.c.) nicotine injection (2 mg/kg, four injections daily) for 14 days. Daily food intake was evaluated for the entire observational period (120 days). Moreover, 30, 60, and 120 days after nicotine withdrawal, we evaluated food intake, nitrite/nitrate levels, and nitric oxide synthase (NOS) activity and expression in the hypothalamus after food deprivation (24 h). In animals in which nicotine dependence was induced (NM), daily food intake was similar to that of controls (M). However, following food deprivation, NM mice showed i) a significant increase in food intake, ii) changes in weight gain and in hypothalamic nitrite/nitrate levels, and iii) enhancement of hypothalamic neuronal NOS (nNOS) activity. Results indicate that high doses of nicotine producing dependence induce long-term changes in feeding behavior consequent to food deprivation associated to alterations in the brain nitrergic system.