Evaluation of Chronic Oral Nicotine Treatment in Food Consumption, Body Weight and [125I Epibatidine Binding in Adult Mice - Juniper Publishers
JUNIPER PUBLISHERS-OPEN ACCESS JOURNAL OF TOXICOLOGY
Evaluation
of Chronic Oral Nicotine Treatment in Food Consumption, Body Weight and [125I
Epibatidine Binding in Adult Mice
Authored by Ursula H Winzer-Serha
Abstract
Despite its
abuse potential, nicotine, acting on nicotinic acetylcholine receptor, has
possible medicinal uses, 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 300μg/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 300μg/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.
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