THE STRESS-RELEASING, BUT NOT CORTICOTROPIN-RELEASING HORMONE-INDUCED ACTIVATION OF THE PITUITARY-ADRENAL AXIS IN MAN IS BLOCKED BY ALPRAZOLAM

A number of experimental studies clearly suggest that benzodiazepines attenuate the corticotropin-releasing hormone (CRH) secretion possibly through inhibitory GABAergic neurons. There is some evidence that benzodiazepines act to inhibit stress-induced activation of the hypothalamic-pituitary-adrenal axis. A comparison of the effects of a benzodiazepine on the stress- and CRH-induced activation in man has not been undertaken so far. We thus investigated the effects of the triazolobenzodiazepine alprazolam on both the stress- and CRH-induced changes in ACTH, cortisol, and prolactin secretion in ten healthy volunteers. In addition, hemodynamic parameters were studied. The subjects received either alprazolam (0.5 mg orally) or placebo 90 min prior to administration of CRH (100 ug i.v.) and to the performance of a mental stress technique. Blood samples, blood pressure and heart rate were taken every 15 min. The administration of alprazolam led to a highly significant attenuation of the ACTH increase following the stress interview. While ACTH increased from 12.4 to 26.7 pg/ml 15 min after the stress procedure in the placebo condition, there was almost no increase following alprazolam intake. An identical effect was found for cortisol secretion. Basal levels of prolactin were slightly enhanced in the alprazolam situation, while the stress-induced increase was not attenuated. Basal and stimulated systolic and diastolic blood pressure levels and heart rate were also significantly attenuated by alprazolam intake. Following administration of CRH, the ACTH augmentation was only slightly affected following alprazolam, while there were no changes in cortisol and prolactin secretion. Our data clearly show, that alprazolam inhibits the stress-induced activation of the pituitary-adrenal axis, while it did not exert major effects after application of exogenous CRH. We thus suggest, that a hypothalamic interaction with a subsequent inhibition of CRH release underlies these observed effects following the administration of alprazolam.