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

The effect 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 (ED50 = 8.6 mumol/kg) and diazepam (ED50 = 8.7 mumol/kg) were equipotent. Administration of 1 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.(ABSTRACT TRUNCATED AT 250 WORDS)