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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 2A  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 ( Gabra1, Gabra2, Gabra2 transcript variant 2, Gabra3, Gabra4, Gabra5, Gabra6, Gabrb1, Gabrb2, Gabrb3, Gabrg1, Gabrg2, Gabrg3, Gabbr1, Gabbr2 ) in rat PFC, and whether testosterone influences GABA A  receptor subunit organization. We studied GABA receptor functions by examining GABA receptor-mediated calcium/calmodulin-dependent kinase signaling genes ( Calm1, Calm2, Calm3, Camk2a, Camk2b, Camk2g, Camk2d, Camk4 ) 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 A  subunit reorganization using cross correlation. Our findings show that expressions of select GABA A  receptor subunits ( Gabra3, Gabra5, Gabra6 ) were significantly upregulated in PFC of T group compared to GDX or C groups. GABA A  receptor subunit organization was different in C, T, and GDX groups. Additionally,  Camk4  expression was significantly downregulated in T compared to C group. Our findings suggest that specific GABA A  receptor subunit expression, their reorganization, and  Camk4 -mediated functions may be associated with testosterone-mediated impulsivity.

frontiers in neuroscience

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