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 psychosocially stressed male tree shrews with diazepam on locomotor activity, marking 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, the 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 therapeutic action of diazepam treatment was followed across 7 days. Twenty-four hours after the last application serum concentrations of diazepam and its major metabolites were determined via HPLC. The results revealed concentrations of 7 ng/ml for diazepam, 106 ng/ml for nordiazepam, 22 ng/ml for temazepam, and 30 ng/ml for oxazepam. Treatment of subordinate animals with diazepam did not reveal a beneficial effect to any of the parameters studied. This contrasts to earlier findings showing that the behavioral and neuroendocrine alterations produced by this stress paradigm are sensitive to chronic treatment with the tricyclic antidepressant clomipramine. The present results support the view that in male tree shrews the state induced by psychosocial stress might be more depression related than anxiety related.