Effects of Diazepam on Low-Frequency and High- Frequency Electrocortical -Power Mediated by α1- and α2-GABAA Receptors

Julian I. Hofmann, Cornelius Schwarz, Uwe Rudolph, Bernd Antkowiak

Research output: Contribution to journalArticle

Abstract

Patterns of spontaneous electric activity in the cerebral cortex change upon administration of benzodiazepines. Here we are testing the hypothesis that the prototypical benzodiazepine, diazepam, affects spectral power density in the low (20–50 Hz) and high (50–90 Hz) -band by targeting GABAA receptors harboring α1- and α2-subunits. Local field potentials (LFPs) and action potentials were recorded in the barrel cortex of wild type mice and two mutant strains in which the drug exclusively acted via GABAA receptors containing either α1- (DZα1-mice) or α2-subunits (DZα2-mice). In wild type mice, diazepam enhanced low γ-power. This effect was also evident in DZα2-mice, while diazepam decreased low γ-power in DZα1-mice. Diazepam increased correlated local LFP-activity in wild type animals and DZα2- but not in DZα1-mice. In all genotypes, spectral power density in the high γ-range and multi-unit action potential activity declined upon diazepam administration. We conclude that diazepam modifies low -power in opposing ways via α1- and α2-GABAA receptors. The drug’s boosting eαect involves α2-receptors and an increase in local intra-cortical synchrony. Furthermore, it is important to make a distinction between high- and low -power when evaluating the effects of drugs that target GABAA receptors.

Original languageEnglish (US)
Article number3486
JournalInternational journal of molecular sciences
Volume20
Issue number14
DOIs
StatePublished - Jul 2 2019

Keywords

  • Aminobutyric acid(A) receptors
  • Benzodiazepine
  • Electroencephalogram
  • GABA(A)-receptor subtypes
  • Gamma-power
  • Hypnotic

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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