Increased dopaminergic and 5‐hydroxytryptaminergic activities in male rat brain following long‐term treatment with anabolic androgenic steroids

The effects of treating groups of rats with four different anabolic androgenic steroids (AAS) (testosterone, nandrolone, methandrostenolone, and oxymetholone) on 5‐hydroxytryptamine (5‐HT) and dopamine (DA) neurones in different brain regions were examined. The AAS was injected six times with 1 week's interval and the rats were sacrificed 2 days after the final injection. 5‐HT and its metabolite 5‐hydroxyindoleacetic acid (5‐HIAA), DA and its metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured. The effect on DA and 5‐HT synthesis rate was analysed as the accumulation of 3,4‐dihydroxyphenyl‐alanine (DOPA) and 5‐hydroxytryptophan (5‐HTP), respectively, after inhibition of the amino acid decarboxylase with NSD‐1015 (3‐hydroxy‐benzylhydrazine dihydrochloride). Additionally, the monoamine oxidase (MAO) activity was analysed in the hypothalamus. The DOPAC+HVA/DA ratio was increased in the striatum in all treatment groups. However, the synthesis rate of DA was significantly increased only in the methandrostenolone treated group. The 5‐HIAA/5‐HT ratio was increased in all treatment groups in the hippocampus, in the frontal cortex in the methandrostenolone‐treated animals and in the hypothalamus in the testosterone‐ and oxymetholone‐treated rats, while the 5‐HT synthesis rate was not affected by the AAS‐treatments. The MAO‐A activity was increased in the oxymetholone‐treated rats while the other treatment groups were unaffected. The MAO‐B activity was not changed. The results indicate that relatively high doses of AAS increase dopaminergic and 5‐hydroxytryptaminergic metabolism in male rat brain, probably due to enhanced turnover in these monaminergic systems. British Journal of Pharmacology (1999) 126, 1301–1306; doi:10.1038/sj.bjp.0702412