The actions of diazepam and serotonergic anxiolytics vary according to the gender and the estrous cycle phase.

The anxiolytic effect of diazepam (0.5, 1.0 and 2.0 mg/kg), buspirone (2.5 and 5.0 mg/kg), indorenate (2.5 and 5.0 mg/kg) and ipsapirone (5.0 and 10.0 mg/kg) was evaluated in male and female rats during the proestrus and metestrus phases. The burying behavior test was used to measure the anxiety levels. In this test, increases in the behavior latency are interpreted as prolonged reactivity, while reductions in the burying behavior are considered to reflect anxiolytic states. Diazepam increases in burying behavior latency were consistently higher than those observed after serotonergic anxiolytics. Buspirone, at no dose tested, affected the burying behavior latency, while indorenate and ipsapirone had only minor effects. Male individuals were more sensitive than females to the actions of diazepam on burying behavior. The serotonergic anxiolytics produce similar responses in both sexes. Metestrus females were much less sensitive to the action of all anxiolytics on burying behavior latency than proestrus females. Proestrus females were highly sensitive to the actions of diazepam on burying latency as compared both with males and metestrus females. Data show that a larger gender and within females variation occurs after treatment with diazepam as compared with the serotonergic anxiolytics. The results are discussed considering the relationships between ovarian hormones and the GABA-benzodiazepinic and serotonergic systems.