Evaluation of Chronic Oral Nicotine Treatment in Food Consumption, Body Weight and [125I] Epibatidine Binding in Adult Mice

Abstract

Despite its abuse potential, nicotine, acting on nicotinic acetylcholine receptor, has possible medicinal uses, in particular in treating neuro degenerative diseases. Therefore, animal models to evaluate exposure need to be characterized. Administration via drinking water is a stress-free route of administration but often results in low blood nicotine levels. Here we evaluated chronic exposure to low, medium and high concentrations of nicotine in drinking water. Three-month-old C57BL/6 male mice were treated for 23 days with 20, 120 or 300 µg/ml nicotine in 2% saccharin water, corresponding to 5, 30 and 55 mg/kg/d, respectively. Food intake and body weight were monitored, blood nicotine and cotinine levels, and 125I-epibatidine-binding sites were determined at day 23.Average blood cotinine levels of 11.7, 151.8 and 192.0 ng/ ml were detected in mice receiving the low, medium and high dose, respectively. In contrast, nicotine was only consistently measured in the group receiving 300 µg/ml, with an average blood level of 6.2 ng/ml and was the only treatment group to exhibit significantly decreased food intake (p=0.005) and body weight (p=0.043), as well as increased I125-epibatidine binding in cortex (p=0.055) and hippocampus (p = 0.019). We evaluated possible effects of chronic nicotine (300µg/ml) exposure on anxiety-like behavior using the open field test. An anxiolytic effect was found compared to controls and there was no evidence for anxiogenic effects of chronic nicotine. Thus, a high concentration of nicotine in drinking water was necessary to achieve consistent blood nicotine levels in mice, which correlated with markers considered hallmarks of chronic nicotine treatment.