Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice - PubMed (original) (raw)

Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice

Barbara J Caldarone et al. Neurosci Lett. 2008.

Abstract

Smoking appears to increase overall levels of stress, despite self-reports that men and women smoke to control symptoms of anxiety. The overall incidence of anxiety disorders is also significantly higher in women. This study examined whether behavioral sensitivity to chronic nicotine varies across sexes in mice. Male and female C57BL/6J mice were exposed chronically to nicotine in the drinking water (50, 100, or 200 microg/ml) and tested for locomotor activation and anxiety-like behavior in the elevated plus maze (EPM). Female mice were less sensitive to the locomotor activating effects of chronic nicotine. Whereas both males and females showed increases in locomotor activity at the highest (200 microg/ml) concentration of nicotine, only males showed locomotor activation at the middle (100 microg/ml) concentration. The decreased sensitivity in females could not be explained by reduced nicotine intake compared to males. In the EPM, nicotine produced an anxiogenic-like response in females, but had no effect in males. Treatment with the high (200 microg/ml) dose of nicotine reduced the amount of time spent in the open arms of the EPM in female, but not male mice. No differences in the anxiogenic-like response to chronic nicotine was observed between beta2-subunit knockout and wildtype mice, suggesting that beta2-subunit containing nicotinic receptors do not mediate the anxiogenic-like response to chronic nicotine in females. This shows that female mice have an anxiogenic-like response to chronic nicotine, but are less sensitive to nicotine's psychostimulant properties, which may be related to the increased relapse to smoking following abstinence in women.

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Figures

Figure 1

Figure 1

Nicotine has anxiogenic-like effects in the EPM in female C57BL/6J mice. Female (A,C) and male (B,D) mice were treated chronically with saccharin or nicotine (200 µg/ml) in their drinking water and mean (±SEM) %time spent in open arms (A,B) and number of entries into closed arms (C,D) are shown. Time in open arms ANOVA: significant drug x sex interaction (F(1,72)=4.9, p<0.05). Females treated with nicotine spent significantly less time in the open arms than females treated with saccharin (Tukey post hoc test). Number of entries into closed arms ANOVA: significant sex x drug interaction (F(1,72)=4.5, p<0.05). No differences in closed arm entries between females treated with saccharin or nicotine (Tukey post hoc test). *p<0.05

Figure 2

Figure 2

Male C57BL/6J mice are more sensitive to locomotor stimulatory effects of nicotine than female mice. Mice received saccharin, 50, 100, or 200 mg/ml nicotine chronically in their drinking water. Mean (±SEM) beam breaks for female (A) and male (B) mice for one hour during the second burst of homecage activity is shown. The maximum hour of activity between 5–8am was averaged across 3 days. ANOVA: significant main effect of sex (F(1,116)=17.5, p<0.0001) and nicotine dose (F(3,116)=5.8, p<0.001). Female mice treated with 200 mg/ml nicotine were more active than the female saccharin control group. Male mice treated with both 100 and 200 mg/ml of nicotine were more active than male saccharin treated controls (*p<0.05 vs. vehicle, Tukey post hoc tests).

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