The Stress-, but Not Corticotropin-Releasing Hormone-Induced Activation of the Pituitary-Adrenal Axis in Man is Blocked by Alprazolam

Abstract

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Temazepam Triggers the Release of Vasopressin into the Rat Hypothalamic Paraventricular Nucleus: Novel Insight into Benzodiazepine Action on Hypothalamic–Pituitary–Adrenocortical System Activity During Stress

“…This is in line with previous studies which were predominantly based on the analysis of plasma corticosterone concentrations (Bruni et al, 1980;Schürmeyer et al, 1988;Owens et al, 1989Owens et al, , 1993Kalogeras et al, 1990;Breier et al, 1991Breier et al, , 1992Schuckit et al, 1992;Torpy et al, 1993Torpy et al, , 1994Rohrer et al, 1994;Korbonits et al, 1995;Arvat et al, 1998Arvat et al, , 1999Skelton et al, 2000). However, in contrast to corticosterone, changes in plasma ACTH can be directly linked to the secretory activity of the parvocellular neurons of the PVN: AVP and CRH are secreted as releasing hormones from these neurons into the pituitary portal blood to synergistically stimulate the secretion of ACTH from the anterior pituitary (Aguilera and Rabadan-Diehl, 2000;Aguilera et al, 2001).…”

Effects of alprazolam and lorazepam on catecholaminergic and cardiovascular activity during supine rest, mental load and orthostatic challenge

“…Reduced BP after ALP administration is consistent with other reports in the literature [Risby et al 1989;Linnoila et al 1990;Rohrer et al 1994 (alprazolam: 0.5 mg);McLeod et al 1990], although some studies observed no effect [Stratton and Halter 1985;Osman et al 1993 (alprazolam: 0.003, 0.007, 0.02 mg/kg, intravenously)]. The unaffected MBP responses to mental and physical stress are in accordance with other studies, where no or a very modest influence of ALP on the MBP response was described [Stratton and Halter 1985;Breier et al 1991;Crowe McCann et al 1992 (0.5 mg alprazolam, orally); Rohrer et al 1994]. HR during supine rest and the HR response during the mental and physical tasks were not affected by ALP.…”

“…Comparable findings for HR during supine rest have been observed in several studies (Stratton and Halter 1985;Linnoila et al 1990;Osman et al 1993), although Risby et al (1989) described a slight increase. HR, obtained while subjects were in a sitting position, was reported to decrease after ALP administration (McLeod et al 1990;Rohrer et al 1994). The findings regarding the influences of ALP on task induced HR increases are divergent.…”

Naloxone decreases the inhibitory effect of alprazolam on the release of adrenocorticotropin/cortisol induced by physical exercise in man

“…In man, ALP modulates the ACTH/cortisol response to various stimuli such as metabolic changes, mental stress, metyrapone, naloxone and hypoglycaemia [2][3][4][5][6]. Physical exercise is a classical stimulus for ACTH/cortisol release in humans.…”