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 other behavioral responses. Acquisition of a conditioning avoidance response (CAR) and spontaneous motor behaviors were assessed in intact male, in intact diestrous and estrous females, and in ovariectomized (OVX) rats injected with estradiol (2 microg/rat, SC) or progesterone (5 mg/rat, SC). A higher dose (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 and in OVX rats injected with estradiol. These effects on conditioning avoidance were not accompanied with equivalent changes in spontaneous motor behaviors. Motor activity and grooming behavior decreased in all experimental groups after administration of 1.0 mg/kg of diazepam. On the contrary, diazepam 0.25 mg/kg increased motor activity in estrous, OVX + estradiol, and OVX + progesterone rats after, whereas grooming behavior was not affected in any group. These findings suggest a physiological influence of ovarian steroid hormones in modifying the benzodiazepine effects on conditioning avoidance 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.
Díaz-Véliz
G
G
Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, P. O. Box 16038, Santiago-9, Chile.
Butrón
S
S
Benavides
M S
MS
Dussaubat
N
N
Mora
S
S
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D004971:Estrus / Q000502:physiology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D014151:Anti-Anxiety Agents; D012739:Gonadal Steroid Hormones; D011374:Progesterone; D004958:Estradiol; D003975:Diazepam