Gender, estrous cycle, ovariectomy, and ovarian hormones influence the effects of diazepam on avoidance conditioning in rats

This study examines whether the hormonal condition of the rat modifies the effects of diazepam (0.25 and 1.0 mg/kg) on avoidance conditioning and othe r behavioral responses. Acquisition of a conditioning avoidance response (C AR) and spontaneous motor behaviors were assessed in intact male, in intact diestrous and estrous females, and in ovariectomized (OVX) rats injected w ith estradiol (2 mu g/rat, SC) or progesterone (5 mg/rat, SC). A higher dos e (1.0 mg/kg) of diazepam significantly impaired the acquisition of CARs in diestrous, OVX, OVX + progesterone, and male rats. Conversely, both doses of diazepam significantly improved the acquisition of CAR in estrous rats a nd in OVX rats injected with estradiol. These effects on conditioning avoid ance were not accompanied with equivalent changes in spontaneous motor beha viors. Motor activity and grooming behavior decreased in ail experimental g roups after administration of 1.0 mg/kg of diazepam. On the contrary, diaze pam 0.25 mg/kg increased motor activity in estrous, OVX + estradiol, and OV X + progesterone rats after, whereas grooming behavior was not affected in any group. These findings suggest a physiological influence of ovarian ster oid hormones in modifying the benzodiazepine effects on conditioning avoida nce and motor activity. The results are discussed considering that ovarian steroids may interact with diazepam on the GABA(A)/benzodiazapine/chloride ionophore complex, modifying the coupling between benzodiazepine sites and GABA(A) receptors. (C) 2000 Elsevier Science Inc.