AUTHOR=Agrawal Juhee , Dwivedi Yogesh 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=14

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.600099

DOI=10.3389/fnins.2020.600099

ISSN=1662-453X

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