Lack of Sex Differences in Anxiety Behaviors During Precipitated Benzodiazepine Withdrawal in Rats

Abstract

Nonprecipitated benzodiazepine (BZ) withdrawal has been reported to increase anxiety levels in rats. The present experiment determined if gender or hormonal status would modulate putative changes in anxiety-related behaviors during precipitated BZ withdrawal in rats. Intact and gonadectomized male and female rats were treated for 4 weeks with empty or diazepam (DZ)-filled silastic capsules. Animals were injected with the BZ antagonist flumazenil (RO15-1788; 5 mg/kg, i.p.) or vehicle, and immediately placed on the elevated plus-maze. Following the 10-min behavioral test, rats were decapitated and trunk blood was collected to measure corticosterone and gonadal hormone levels. During precipitated BZ withdrawal rats showed significantly decreased percent open-arm time; however, this finding was confounded by a significant decrease in activity levels (e.g., closed-arm entries and total-arm entries). Precipitated BZ withdrawal did not significantly attenuate percent open-arm entries, which factors out drug-induced changes in activity levels, compared to vehicle control animals. Overall, the results of this experiment suggest that precipitated BZ withdrawal does not significantly increase anxiety levels when compared to control animals.