Effects of sub-chronic nandrolone administration on hormonal adaptive response to acute stress in rats

Summary Androgenic-anabolic steroid (AAS) misuse has been associated with depression. It has been proposed that stress has a role in depression and that serotonin is involved in both endocrine responses to stress and depressive physiopathology. Although reports demonstrate that AAS chronic administration modifies components of stress-responsive hypothalamic–pituitary–adrenal axis (HPAA), no study has evaluated AAS effect on the response to stressful stimuli. We studied the effects of the subchronic administration (once a day for 14 days in rats) of a supratherapeutical dose of nandrolone decanoate (ND) on HPAA and cortical serotoninergic system response to acute restraint stress (RS). Acute RS produced the following effects: increase in CORT (in blood) and ACTH (both in blood and in pituitary corticotropes), GR depletion in hippocampus and hypothalamus cytosol and GR translocation in hippocampus nuclear fraction, cortical serotonin re-uptake stimulation and hippocampus cytosolic ERK2 activation. ND by itself, i.e. in non-stressed rats, did not modify these parameters, except for a decrease of plasma CORT and ACTH levels and an increase in hippocampus cytosolic phospho-ERK1/2. On the contrary, in stressed rats ND affected stress-induced plasma ACTH increase and prevented all other above reported stress effects, except the increase in pituitary ACTH positive cell density. Our results show that the prolonged administration of a supratherapeutical dose of ND in rats, albeit did not affect in a notable way HPAA and serotonin transporter activity in the absence of stress, may deregulate the stress-induced hormonal cascade which plays a crucial role in depressive psychopathology.