Repeated anabolic androgenic steroid treatment causes antidepressant-reversible alterations of the hypothalamic-pituitary-adrenal axis, BDNF levels and behavior.

Abuse of anabolic androgenic steroids (AASs) is frequently associated with changes in mood, including depression. However, the nature of this association is still largely unexplored. As a model of AAS abuse, we used male adult rats injected for 4 weeks with either nandrolone or stanozolol at daily doses (5 mg/kg, s.c.) that are considered equivalent to those abused by humans on a milligram per kilogram of body weight basis. AAS treatment reduced levels of brain-derived neurotrophic factor in the hippocampus and prefrontal cortex, reduced the expression of low-affinity glucocorticoid receptors in the hippocampus, and increased morning trough basal plasma corticosterone levels. All these changes have been related to the pathophysiology of major depressive disorder. Accordingly, rats treated with nandrolone or stanozolol showed an increased immobility time in the forced swim test, which is widely used for the screening of antidepressant drugs. All effects produced by AASs were prevented by co-administration with the classical antidepressant, chlorimipramine. The evidence that supraphysiological doses of AASs induce changes indicative of a depressive state in normal rats, raises the concern that AAS abuse in humans may cause depression regardless of exposure to stress or other risk factors.