REGULATION OF GABAA RECEPTORS BY PROLONGED EXPOSURE OF CORTICAL NEURONS TO BENZODIAZEPINES IS MEDIATED BY A CALCIUM SIGNALING PATHWAY

L. CAROLINA GONZÁLEZ GÓMEZ; SARA SANZ BLASCO; NELSY BEATRIZ MEDINA; MARÍA CLARA GRAVIELLE

Mar del Plata

Congreso; Reunión Anual de las Sociedades de Biociencias; 2022

Sociedad Argentina de Investigaciones Clínicas

The clinical use of benzodiazepines has been limited by the development of tolerance to most of their pharmacological effects. In previous studies, we demonstrated that the prolonged exposure of rat cortical neurons to diazepam (DZ) produces a transcriptional repression of the GABAA receptor α1 subunit gene and this effect is prevented in the presence of nifedipine, an inhibitor of L-type voltage gated calcium channels (L-VGCC). The aim of this work was to investigate the signaling cascade triggered by the prolonged treatment with DZ that results in the regulation of the GABAA receptor. To this end, we exposed rat primary neuronal cultures to DZ (1 μM) for 48h in the presence or absence of different inhibitors. Results from this study indicated that the DZ-induced decrease in the mRNA and protein levels of the α1 subunit was inhibited in the presence of 1 mM EGTA (p