Brain Nerve Growth Factor Unbalance Induced by Anabolic Androgenic Steroids in Rat.

PURPOSE: Anabolic androgenic steroids (AASs) are synthetic androgen-like compounds which are abused in sport communities despite their side effects. Nerve growth factor (NGF) influences neuronal differentiation and survival, and also mediates higher brain functions such as learning and memory. Changes in NGF expression have been implicated in neurodegenerative disorders, including Alzheimer's disease. Hence, we decided to study the effect of chronic AASs exposure on brain NGF profile, NGF-dependent cholinergic function and related behavioral performance. METHODS: Male Wistar rats were injected for 4 weeks with either nandrolone or stanozolol at daily doses (5.0 mg/kg, s.c.) that are considered equivalent to those abused by humans. NGF levels and NGF receptor (TrkA and p75NTR) expression were measured in the hippocampus and in the basal forebrain. Choline acetyltransferase expression was evaluated in basal forebrain. Spatial learning and memory were assessed using the Morris water maze. RESULTS: AASs treatment caused region-specific changes in the expression of NGF and its receptors. Both nandrolone and stanozolol increased NGF levels in the hippocampus and reduced NGF levels in the basal forebrain, reduced p75NTR expression in the hippocampus, and failed to affect TrkA expression in the basal forebrain. Finally, AASs treatment reduced the expression of choline acetyltransferase in the basal forebrain and impaired the behavioral performance in the Morris water maze. CONCLUSION: The evidence that supraphysiological doses of AASs cause neurotrophic unbalance and related behavioral disturbances, raises the concern that AASs abuse in humans may affect mechanisms that lie at the core of neuronal plasticity.