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

Br J Pharmacol. 1999 Mar;126(6):1301-6. doi: 10.1038/sj.bjp.0702412.

Abstract

1. 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. 2. 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. 3. 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. 4. 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. 5. 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.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • 5-Hydroxytryptophan / drug effects
  • 5-Hydroxytryptophan / metabolism
  • Anabolic Agents / pharmacology*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dihydroxyphenylalanine / drug effects
  • Dihydroxyphenylalanine / metabolism
  • Dopamine / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Homovanillic Acid / metabolism
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Methandrostenolone / pharmacology
  • Monoamine Oxidase / drug effects
  • Monoamine Oxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Synaptosomes / drug effects
  • Synaptosomes / enzymology
  • Time Factors

Substances

  • Anabolic Agents
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Dihydroxyphenylalanine
  • 5-Hydroxytryptophan
  • Methandrostenolone
  • Monoamine Oxidase
  • Dopamine
  • Homovanillic Acid