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.
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