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

L. CAROLINA GONZÁLEZ GÓMEZ; SANZ BLASCO S; NELSY BEATRIZ MEDINA; MARIA 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 oftolerance to most of their pharmacological effects. In previous studies, wedemonstrated that the prolonged exposure of rat cortical neurons to diazepam(DZ) produces a transcriptional repression of the GABA A receptor α1 subunitgene 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 toinvestigate the signaling cascade triggered by the prolonged treatment with DZthat results in the regulation of the GABA A receptor. To this end, we exposed ratprimary neuronal cultures to DZ (1 μM) for 48h in the presence or absence ofdifferent inhibitors. Results from this study indicated that the DZ-induceddecrease in the mRNA and protein levels of the α1 subunit was inhibited in thepresence of 1 mM EGTA (p