Abstract

Benzodiazepine administration has been associated with alterations in neuroendocrine function both in experimental animals and in humans. Clinical and laboratory data indicate that the beta-carbolines, a class of active benzodiazepine receptor inverse agonists, cause behavioral and neuroendocrine changes characteristic of anxiety and stress. In contrast, the "classic" benzodiazepine receptor agonists such as diazepam can reduce anxiety and inhibit stress-induced increases in anterior pituitary hormone secretion. Although the site of action and mechanisms by which benzodiazepines alter anterior pituitary hormone secretion are still under investigation, evidence suggests that the effects are mediated in the brain, primarily through actions at benzodiazepine receptors in the hypothalamus. The benzodiazepines may act at GABA-coupled benzodiazepine receptors in the hypothalamus or other regions of the brain to potentiate the effects of endogenous GABA. It also is believed that brain monoamines may modulate the effects of endogenous GABA. Brain monoamines have also been reported to modulate the effects of benzodiazepines on stress-induced hypothalamic-pituitary-adrenocortical function. Direct effects of the benzodiazepines on central- and peripheral-type benzodiazepine receptors in the anterior pituitary have also been documented.