Anabolic Androgenic Steroids and the Brain : Studies of Neurochemical and Behavioural Changes Using an Animal Model

A new group of anabolic androgenic steroid (AAS) users has developed during the last two decades. This group consists primarily of young men interested in improving their physical appearance. Within this group, AAS are sometimes used together with other illicit drugs, alcohol and nicotine. Brutal and violent crimes have been committed under the influence of AAS, possibly because of AAS psychiatric side effects, ranging from increased aggression and psychosis to depression. Unfortunately, the biochemical mechanisms behind these effects are poorly understood. In this thesis we used an animal model to study biochemical and behavioural effects of chronic AAS treatment (15 mg/kg/day of nandrolone decanoate for 14 days). The effect on the endogenous opioid peptides and the expression of immediate-early gene protein Fos in various brain regions were studied using radioimmunoassay and immunohistochemistry, respectively. In addition, we studied AAS effect on voluntary alcohol consumption and defensive behaviours, including aggression. The results show that AAS enhance endogenous opioid activity and Fos expression in brain regions regulating reward, aggression and disinhibitory behaviours. An imbalance between two opioid systems with generally opposing effects, the enkephalins with euphoric and the dynorphins with dysphoric effects, was also found. This implies that AAS alter the ability to maintain a stable state of mind and the response to other drugs of abuse. The AAS pre-treated animals enhanced their alcohol intake, were more aggressive and showed lower fleeing and freezing reaction than the controls. In addition, AAS enhanced amphetamine-induced aggression when the amphetamine was given three weeks after the last AAS injection. The behavioural and biochemical results found in this thesis, support the hypothesis that use of AAS might lead to the development of dependence and may induce changes in the brain leading to disinhibitory behaviours