Elsevier

Neuroscience Letters

Volume 439, Issue 2, 11 July 2008, Pages 187-191
Neuroscience Letters

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

https://doi.org/10.1016/j.neulet.2008.05.023Get rights and content

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 μg/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 μg/ml) concentration of nicotine, only males showed locomotor activation at the middle (100 μg/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 μg/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 β2-subunit knockout and wildtype mice, suggesting that β2-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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Acknowledgements

We would like to thank Haleh Nadim and Dr. Peter Jatlow for help with the cotinine measurements. These studies were supported by grants DA00436, DA10455, DA14241 and AA15632 from the National Institutes of Health.

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    1

    These authors contributed equally to the work.

    2

    Present address: Department of Psychology, University of Sussex, Brighton, UK.

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