Brain nitric oxide metabolites in rats preselected for nicotine preference and intake

•Rats were exposed to oral nicotine choice starting at adolescence or adulthood.•Brain nitrate+nitrite determined in rats with maximum/minimum nicotine preference.•Control rats received only water from both bottles, naïve rats were group housed.•Isolation stress increased NO metabolites in the hippocampus (naïve–control).•Preference had no effect; adolescent-onset rats had higher NO activity in frontal cortex. Nicotine addiction is a serious health problem resulting in millions of preventable deaths worldwide. The gas messenger molecule nitric oxide (NO) plays a critical role in addiction, and nicotine increases nitric oxide metabolites (NOx) in the brain. Understanding the factors which underlie individual differences in nicotine preference and intake is important for developing effective therapeutic strategies for smoking cessation. The present study aimed to assess NO activity, by measuring its stable metabolites, in three brain regions that express high levels of nicotinic acetylcholine receptors in rats preselected for nicotine preference. Rats (n=88) were exposed to two-bottle, free choice of oral nicotine/water starting either as adolescents or adults; control animals received only water under identical conditions. Following 12 or six weeks of exposure, levels of NOx (nitrite+nitrate), were determined in the hippocampus, frontal cortex, and amygdala. Since the rats were singly housed during oral nicotine treatment, naïve rats were also included in the study to evaluate the effect of isolation stress. Isolation stress increased NOx in the hippocampus. Nicotine preference did not have a significant effect on NO activity, but rats with adolescent exposure had higher NOx levels in the frontal cortex compared to adult-onset rats. Our findings suggest that nicotine exposure during adolescence, regardless of the amount of nicotine consumed, results in higher NO activity in the frontal cortex of rats, which persists through adulthood.