Plasma corticosterone responses to stress following chronic oral administration of diazepam in the rat

Abstract

The effect of daily, oral administration of diazepam on plasma corticosterone responses to stressors of varying intensity was investigated. In rats exposed to the mild stress of noise, diazepam, 10 mg kg-1 but not 1.0 or 0.1 mg kg-1, reduced plasma corticosterone concentrations by 30% in comparison with controls. However, in rats exposed to the more severe stressors, foot-shock or immobilization, none of these doses of diazepam reduced plasma corticosterone responses. In unstressed rats, diazepam 10 mg kg-1 raised plasma corticosterone concentrations. It is suggested that plasma corticosterone concentrations are not a reliable indicator of the tranquillizing effect of diazepam during stress.

Effects of prenatal exposure to a mild chronic variable stress on body weight, preweaning mortality and rat behavior

“…This is supported also by the fact that chronic prenatal stress decreases benzodiazepine binding as well as 3H-5-HT binding in the hippocampus of rat pups (2,24). Both the neurotransmitter systems and the hippocampus are known to be involved in emotional regulation (23,25).…”

“…This stress model causes a consumatory and motivational deficit, which has been interpreted as anhedonia (12,16,18), blocks the behavioral activation induced by noise stimulation (15), blocks holeboard exploration (13), increases anxiety levels in emergence tests (17), impairs forced swimming behavior, i.e., increases behavioral despair (13,17) and increases basal levels of the stress-sensitive hormones, corticosterone and prolactin in both male and female rats (17,23). This syndrome, which lasts up to day 4 post-treatment (17), has been used as an animal model of human depression reactions (15)(16)(17).…”

Drug actions on delayed-type hypersensitivity in rats with developing and established adjuvant arthritis

“…The anxiolytic agent diazepam [23] and the steroid receptor antagonist RU38486 [24] were studied in an attempt to reveal a regulatory role for anxiety, stress and endogenous steroid release in AA and the associated DTH. However, these agents failed to significantly modify disease severity or DTH perhaps indicating inappropriate dosing schedules or stress intensity [23][24][25].…”

Neuroendocrine markers of CNS drug effects.

“…Diazepam has been shown to reduce ACTH output in man (Rees, 1970) and to reduce basal cortisol secretion in animals at low doses although in high doses cortisol secretion in animals is increased (Barlow, Knight & Sullivan, 1979 This finding has been replicated in patients with many diagnoses (General Practitioner Clinical Trials, 1970) and although the drug has been used in the treatment of anorexia nervosa systematic studies of its value in that condition have been few (Halmi & Goldberg, 1978). Endocrinological effects of cyproheptadine in man have been little studied but it has been found to reduce the growth hormone response to hypoglycaemia in normal volunteers (Bivens, Lebovitz & Feldman, 1973) and to suppress sleep related GH and cortisol release (Chihara, Kato, Maeda, Matsukara & Imura, 1976 (1979).…”