DIAZEPAM-INDUCED TRANSCRIPTIONAL REGULATION OF GABAA RECEPTOR ALPHA1 SUBUNIT GENE VIA L-TYPE VOLTAGE-GATED CALCIUM CHANNEL ACTIVATION IN RAT CEREBROCORTICAL NEURONS

NELSY BEATRIZ MEDINA; MARÍA FLORENCIA FOITZICK; LUCÍA CANDELA IGLESIAS GARCÍA; MARÍA CLARA GRAVIELLE

Mar del Plara

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

SAIC SAFE SAB SAP NanoMed ar AACyTAL

GABA-A receptors are targets of different pharmacologically relevant drugs, such as barbiturates, benzodiazepines, and anesthetics. In particular, benzodiazepines are prescribed for the treatment of anxiety, sleep disorders, and seizure disorders. Prolonged activation of GABA-A receptors by endogenous and exogenous modulators induces adaptive changes that lead to tolerance. For example, chronic administration of benzodiazepines produces tolerance to most of their pharmacological actions, limiting their usefulness. The mechanism of tolerance is still unknown. We have previously demonstrated that chronic diazepam administration in rats result in tolerance to the sedative and anxiolytic effects which is accompanied with a decrease in the interactions between GABA and benzodizepine binding sites (uncoupling) in cerebral cortex. The aim of this work was to investigate the molecular mechanism of benzodiazepine tolerance in an in vitro model of primary neuronal cultures from rat cerebral cortex. The exposure of cultured neurons to diazepam for 48 h produced a 40 % uncoupling (p