Neurosteroids regulate mouse aggression induced by anabolic androgenic steroids

Neuroreport. 2006 Oct 2;17(14):1537-41. doi: 10.1097/01.wnr.0000234752.03808.b2.

Abstract

Anabolic androgenic steroid abuse triggers impulsive aggression, anxiety, and depression, which suggests a dysfunction of GABAergic neurotransmission. Socially isolated female mice that have received testosterone propionate (1.45 micromol/kg) treatment for 3 weeks during social isolation express aggression, neurosteroid downregulation, and changes in the cortical mRNA expression of several gamma-aminobutyric acid type A receptor subunits (alpha1, alpha2, gamma2 are decreased by 30-40%, and alpha4 and alpha5 are increased by 50%). Administration of allopregnanolone or the potent selective brain steroidogenic stimulant S-norfluoxetine, in doses (1.8-3.6 micromol/kg) that fail to inhibit 5-hydroxytryptamine reuptake, normalizes olfactory bulb neurosteroid level downregulation and abolishes aggression. This work underscores the role of neurosteroids in the regulation of aggression elicited by testosterone propionate in socially isolated female mice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / drug effects*
  • Androgens / pharmacology*
  • Anesthetics / pharmacology
  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects
  • Brain / metabolism
  • Brain Chemistry / drug effects
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Fluoxetine / analogs & derivatives
  • Fluoxetine / pharmacology
  • Gene Expression Regulation / drug effects
  • Male
  • Mice
  • Motor Activity / drug effects
  • Pregnanolone / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Serotonin / metabolism
  • Sex Factors
  • Social Isolation
  • Testosterone / pharmacology*
  • Time Factors

Substances

  • Androgens
  • Anesthetics
  • RNA, Messenger
  • Receptors, GABA-A
  • Fluoxetine
  • Serotonin
  • Testosterone
  • Pregnanolone
  • norfluoxetine