GABA Receptor Subunit Transcriptional Regulation, Expression Organization, and Mediated Calmodulin Signaling in Prefrontal Cortex of Rats Showing Testosterone-Mediated Impulsive Behavior.

Testosterone can induce impulsivity, a behavioral impairment associated with various psychiatric illnesses. The molecular mechanisms associated with testosterone-induced impulsivity are unclear. Our earlier studies showed that supraphysiological doses of testosterone to rats induced impulsive behavior, impacted hypothalamic-pituitary-adrenal axis (HPA) and hypothalamic-pituitary-gonadal axis interactions, and altered α adrenergic receptors in prefrontal cortex (PFC). Owing to the importance of GABAergic system in impulsivity and memory, the present study examines whether testosterone-mediated impulsivity is associated with changes in the expression of Gamma-Aminobutyric Acid (GABA) A and B receptor subunit transcripts () in rat PFC, and whether testosterone influences GABA receptor subunit organization. We studied GABA receptor functions by examining GABA receptor-mediated calcium/calmodulin-dependent kinase signaling genes () in the testosterone-induced impulsivity model. Rats were left untreated as controls (C), gonadectomized (GDX), or GDX and injected with supraphysiological doses of testosterone (T). Impulsive behavior was examined using the go/no-go paradigm. Gene expression was studied using qRT-PCR and GABA subunit reorganization using cross correlation. Our findings show that expressions of select GABA receptor subunits () were significantly upregulated in PFC of T group compared to GDX or C groups. GABA receptor subunit organization was different in C, T, and GDX groups. Additionally, expression was significantly downregulated in T compared to C group. Our findings suggest that specific GABA receptor subunit expression, their reorganization, and -mediated functions may be associated with testosterone-mediated impulsivity.