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

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 locomotor activation. 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.

Nicotine Withdrawal Increases Stress-Associated Genes in the Nucleus Accumbens of Female Rats in a Hormone-Dependent Manner

“…This is consistent with findings from other laboratories showing that female rodents display an increase in anxiety-like behavior and plasma corticosterone levels during nicotine withdrawal. [31][32][33][34] The present study also revealed a different pattern of changes in CRF receptor gene expression during nicotine exposure and withdrawal. Specifically, both CRF-R1 and CRF-R2 gene expression was decreased during nicotine exposure in intact females.…”

Placental Cytokine Expression Covaries with Maternal Asthma Severity and Fetal Sex

“…This may be explained by differential binding of nicotine to the nicotinic acetylcholine receptor (58) in the placentae of males and females. There are known sex specific differences in the sensitivity of these nicotinic receptors, where males are more sensitive than females (59). Furthermore, estrogen acts as a natural antagonist at nicotinic receptors, therefore altering the effects of nicotine in females relative to males (60).…”

Sex Differences in Animal Models: Focus on Addiction

“…Nicotine. In a mouse study, continuous nicotine exposure in the drinking water produced an anxiogeniclike response in the elevated plus maze in females but failed to produce an anxiogenic-like response in males during withdrawal (Caldarone et al, 2008). Female rats showed greater adrenocorticotropic hormone levels during nicotine withdrawal.…”