Neurosteroids regulate mouse aggression induced by anabolic androgenic steroids

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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 μmol/kg) treatment for 3 weeks during social isolation express aggression, neurosteroid downregulation, and changes in the cortical mRNA expression of several γ-aminobutyric acid type A receptor subunits (α1, α2, γ2 are decreased by 30–40%, and α4 and α5 are increased by 50%). Administration of allopregnanolone or the potent selective brain steroidogenic stimulant S-norfluoxetine, in doses (1.8–3.6 μmol/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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