Functional changes in GABAA receptor stimulation during the oestrous cycle of the rat

Abstract

1. Slices of rat cuneate nucleus were used to study whether or not gonadal steroids influence the gamma-aminobutyric acid (GABA) system in vivo. Females in different stages of the oestrous cycle as well as steroid-treated (oestrogen, progesterone or both) ovariectomized animals were used. 2. Functional changes in the GABAA receptors were assayed using the effects of potentiators (benzodiazepine, barbiturate) and antagonists (picrotoxin) on the muscimol control dose-response curves. 3. The potentiating effect of the benzodiazepine, flurazepam was unchanged during the oestrous cycle, and the hormone treatments did not alter this effect. 4. During oestrus, an increase was seen in the potentiating effect of the barbiturate (pentobarbitone). This suggests a synergistic effect between barbiturates and gonadal steroids. Progesterone treatment also increased the effect of pentobarbitone. 5. The antagonistic action of picrotoxin was unaffected during the oestrous cycle. However, progesterone (or progesterone and oestrogen) treatment reduced the potency of picrotoxin. 6. This study supports the idea that endogenous steroids (presumably progesterone) affect the GABAA receptors during the oestrous cycle by a mechanism associated with the barbiturate site of the GABAA receptor complex.