Fluctuations in responses to diazepam during the oestrous cycle in the mouse

Administration of diazepam (0.28 mg/kg, IP; 60 min) to male mice or to female mice at oestrus or dioestrus increased the number of transitions made between the light and dark chambers of a test apparatus, a presumed anxiolytic action. However, the same dose of diazepam had no effect on light/dark transitions at late dioestrus, proestrus, or metoestrus II. At metoestrus I, this test dose of diazepam induced a decrease in the number of light/dark transitions and significant changes in other test parameters indicative of an increase in fearfulness or light aversion. Concentrations of diazepam in the brain after intraperitoneal injection were not influenced by the stage of the oestrous cycle, suggesting that the observed changes in responses to diazepam reflect changes in sensitivity to this drug rather than alterations in distribution or metabolism. The results indicate a physiological influence of ovarian steroid hormones on sensitivity to the benzodiazepine tranquilisers.