Diazepam has no beneficial effects on stress-induced behavioural and endocrine changes in male tree shrews

The present study evaluated the effect of subchronic oral treatment of psyc hosocially stressed male tree shrews with diazepam on locomotor activity, m arking behavior, avoidance behavior, and urinary cortisol and noradrenaline . To mimic a realistic situation of anxiolytic intervention, the treatment started 14 days after the beginning of psychosocial stress; at that time, t he stress-induced behavioral and endocrine alterations had been established . The drug (5 mg/kg/day) was administered orally in the morning, while the psychosocial stress continued during the whole treatment period; the therap eutic action of diazepam treatment was followed across 7 days. Twenty-four hours after the last application serum concentrations of diazepam and its m ajor metabolites were determined via HPLC. The results revealed concentrati ons of 7 ng/ml for diazepam, 106 ng/ml for nordiazepam, 22 ng/ml for temaze pam, and 30 ng/ml for oxazepam. Treatment of subordinate animals with diaze pam did not reveal a beneficial effect to any of the parameters studied. Th is contrasts to earlier findings showing that the behavioral and neuroendoc rine alterations produced by this stress paradigm are sensitive to chronic treatment with the tricyclic antidepressant clomipramine. The present resul ts support the view that in male tree shrews the state induced by psychosoc ial stress might be more depression related than anxiety related. (C) 2000 Elsevier Science Inc.