Analysis of GABAA Receptor Function and Dissection of the Pharmacology of Benzodiazepines and General Anesthetics Through Mouse Genetics

Uwe Rudolph, Hanns Möhler

Research output: Contribution to journalReview article

Abstract

GABAA receptors are molecular substrates for the regulation of vigilance, anxiety, muscle tension, epileptogenic activity, and memory functions, and the enhancement of GABAA receptor-mediated fast synaptic inhibition is the basis for the pharmacotherapy of various neurological and psychiatric disorders. Two kinds of GABAA receptor-targeted mutant mice have been generated: (a) knockout mice that lack individual GABAA receptor subunits (α1, α5, α6, β2, β3, γ2, δ, and ρ1) and (b) knockin mice that carry point mutations affecting the action of modulatory drugs [α1(H101R), α2(H101R), α3(H126R), α5(H105R), and β3(N265M)]. Whereas the knockout mice have provided information primarily with respect to the regulation of subunit gene transcription, receptor assembly, and some physiological functions of individual receptor subtypes, the point-mutated knockin mice in which specific GABAA receptor subtypes are insensitive to diazepam or some general anesthetics have revealed the specific contribution of individual receptor subtypes to the pharmacological spectrum of diazepam and general anesthetics.

Original languageEnglish (US)
Pages (from-to)475-498
Number of pages24
JournalAnnual Review of Pharmacology and Toxicology
Volume44
DOIs
StatePublished - Mar 10 2004

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Dissection
General Anesthetics
GABA-A Receptors
Benzodiazepines
Pharmacology
Diazepam
Knockout Mice
Drug therapy
Muscle Tonus
Transcription
Nervous System Diseases
Point Mutation
Psychiatry
Muscle
Anxiety
Genes
Genetics
Data storage equipment
Drug Therapy
Substrates

Keywords

  • Anxiolysis
  • Diazepam
  • Etomidate
  • Knockin mice
  • Knockout mice

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

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