92. PROLONGED EXPOSURE OF CORTICAL NEURONS TO DIAZEPAM INDUCES DOWNREGULATION OF GABAA RECEPTOR α1 SUBUNIT VIA A CALCIUM/ PROTEIN KI- NASE A SIGNALING PATHWAY

GRAVIELLE, MARÍA CLARA; GONZÁLEZ GÓMEZ, LEYDI CAROLINA; SANZ BLASCO, SARA

Mar del Plata

Congreso; SAIC 2023; 2023

Sociedad Argentina de Investigación Clínica

Benzodiazepines exhibit a high therapeutic index and low toxicity inshort-term treatments, however, prolonged administration inducestolerance to most of their therapeutic actions. In previous studies,we demonstrated that the prolonged exposure of rat cortical neuronsto diazepam (DZ) produces a transcriptional repression of theGABAA receptor α1 subunit gene. This regulatory mechanism dependson the activation of L-type voltage gated calcium channels(L-VGCC). The aim of this work was to investigate the signalingcascade triggered by the benzodiazepine-induced stimulation ofcalcium influx that leads to the regulation of the GABAA receptorexpression. To this end, we exposed rat 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 inthe mRNA and protein levels of the α1 subunit was inhibited in thepresence of 1 μM H-89, a protein kinase A (PKA) inhibitor (p