A comparison of the effects of buspirone and diazepam on plasma corticosterone levels in rat

Abstract

The effects of the anxiolytic agents, buspirone and diazepam, on the hypothalamic-pituitary-adrenal axis (HPAA), indicated by changes in the concentration of corticosterone (CS) in plasma, were studied 1 2 , 1, 2, 4, 6, 8 and 24 hr after administration of the drug (i.p.). Samples of plasma were collected in the mid-morning (0930–1130 hr) when activity in the hypothalamic-pituitary-adrenal axis in the rat and control levels of corticosterone were low and were repeated in the afternoon (1400–1600 hr) when activity in the hypothalamic-pituitary-arenal axis and levels of corticosterone were higher. At small doses (1 mg/kg) buspirone had a greater facilitating effect on the hypothalamic-pituitary-adrenal axis than did diazepam. In addition, buspirone had a greater maximum facilitatory effect (477%) on levels of corticosterone than diazepam (345%). However, buspirone (ED 50 = 8.6 μmol/kg) and diazepam (ED 50 = 8.7 μmol/kg) were equipotent. Administration of I mg/kg of buspirone in the morning increased the combined 1 2 and 1 hr circulating levels of corticosterone 75% above control levels. Diazepam, at 1 mg/kg, did not produce any significant changes in levels of corticosterone. Large doses (10 mg/kg) of buspirone increased morning levels of corticosterone by 328% and diazepam increased levels of corticosterone by 265%. During the afternoon small doses of buspirone or diazepam did not significantly alter levels of corticosterone. Large doses of buspirone and diazepam significantly increased levels of corticosterone by 166% and 80%, respectively. Animals stressed by spinning for l min at 30–60 rpm, 15min before decapitation had levels of corticosterone that were 397% higher than the morning, and 238% higher than the afternoon control levels. The effects of spinning stress and the actions of buspirone on the hypothalamic-pituitary-adrenal axis were additive at large doses as buspirone increased levels of corticosterone above stressed controls by 20%.