Corticotropin and cortisol secretion after central 5-hydroxytryptamine-1A (5-HT1A) receptor activation: effects of 5-HT receptor and beta-adrenoceptor antagonists

To explore the involvement of 5-hydroxytryptamine-1A (5-HT1A) receptors in hypothalamic-pituitary-adrenal (HPA) axis regulation, various doses of ipsapirone (IPS), a centrally acting pyrimidinylpiperazine with considerable affinity and selectivity for 5-HT1A recognition sites, were administered to normal subjects. IPS dose-dependently increased plasma ACTH concentrations from -78 +/- 63 to 614 +/- 250 pmol.min/L (P less than 0.01) and plasma cortisol concentrations from -10.8 +/- 2.9 x 10(3) to 21.3 +/- 8.2 x 10(3) nmol.min/L (P less than 0.01) at a dose of 0.3 mg/kg in six men. The nonselective 5-HT receptor antagonist metergoline which acts at both 5-HT1 and 5-HT2 receptors partially blocked the HPA response to IPS in six women and three men. The mean maximal integrated ACTH response decreased from 746 +/- 297 to 40 +/- 146 pmol/min.L (P less than 0.05), and the increase in cortisol was attenuated from 22.9 +/- 9.9 x 10(3) to 11.9 +/- 6.3 x 10(3) nmol.min/L (P less than 0.05). The nonselective beta-adrenergic and selective 5-HT1A/1B receptor antagonist (+/-)pindolol was without effect on basal HPA activity, but completely antagonized the IPS-induced plasma ACTH and cortisol responses. The mean maximal integrated ACTH response decreased to 8.0 +/- 78 pmol.min/L (P less than 0.05), and the cortisol response was reduced to -2.3 +/- 6.5 x 10(3) nmol.min/L (P less than 0.05). The selective beta 1-adrenoceptor antagonist betaxolol did not significantly alter the IPS-induced HPA response.(ABSTRACT TRUNCATED AT 250 WORDS)