Research article summary (published 30 May 2001):

Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice.

Full Abstract

The recent cloning of two GABA(B) receptor subunits, GABA(B1) and GABA(B2), has raised the possibility that differences in GABA(B) receptor subunit composition may give rise to pharmacologically or functionally distinct receptors. If present, such molecular diversity could permit the selective targeting of GABA(B) receptor subtypes specifically involved in pathologies such as drug addiction, spasticity, pain, and epilepsy. To address these issues we have developed a GABA(B1) subunit knockout mouse using gene targeting techniques. In the brains of GABA(B1) null mice, all pre- and postsynaptic GABA(B) receptor function was absent demonstrating that the GABA(B1) subunit is essential for all GABA(B) receptor-mediated mechanisms. Despite this, GABA(B1) null mice appeared normal at birth, although by postnatal week four their growth was retarded and they developed a generalized epilepsy that resulted in premature death. In addition, GABA(B1) heterozygote animals showed enhanced prepulse inhibition responses compared to littermate controls, suggesting that GABA(B1) deficient mice exhibit increased sensorimotor gating mechanisms. These data suggest that GABA(B) receptor antagonists may be of benefit in the treatment of psychiatric and neurological disorders in which attentional processing is impaired. Copyright 2001 Academic Press.

Author information

Author/s: Prosser, H M (HM); Gill, C H (CH); Hirst, W D (WD); Grau, E (E); Robbins, M (M); Calver, A (A); Soffin, E M (EM); Farmer, C E (CE); Lanneau, C (C); Gray, J (J); Schenck, E (E); Warmerdam, B S (BS); Clapham, C (C); Reavill, C (C); Rogers, D C (DC); Stean, T (T); Upton, N (N); Humphreys, K (K); Randall, A (A); Geppert, M (M); Davies, C H (CH); Pangalos, M N (MN);

Affiliation: Genetics Research, Safety Assessment, Laboratory Animal Sciences, Neurology Centre of Excellence for Drug Discovery, Psychiatry Centre of Excellence for Drug Discovery, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, United Kingdom.

Journal and publication information

Publication Type: Journal Article

Journal: Molecular and cellular neurosciences (Mol Cell Neurosci), published in United States. (Language: eng)

Reference: 2001-Jun; vol 17 (issue 6) : pp 1059-70

Dates: Created 2001/06/20; Completed 2001/08/30; Revised 2003/11/14;

PMID: 11414794, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Action Potentials - drug effects; physiology Animals Baclofen - pharmacology Behavior, Animal - physiology Central Nervous System - abnormalities; metabolism; physiopathology Down-Regulation - genetics Epilepsy - congenital; genetics; physiopathology GABA Agonists - pharmacology Gene Targeting - methods Heterozygote Mice Mice, Knockout - abnormalities; anatomy & histology; metabolism

Mice, Knockout - abnormalities; anatomy & histology; metabolism Neural Inhibition - genetics Neurons - cytology; metabolism Phenotype RNA, Messenger - metabolism Radioligand Assay Receptors, GABA-B - deficiency; genetics; metabolism Seizures - congenital; genetics; physiopathology Startle Reaction - drug effects; physiology Synapses - drug effects; metabolism; ultrastructure Synaptic Transmission - drug effects; genetics gamma-Aminobutyric Acid - metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: GABA Agonists (0) ; GABA type B receptor, subunit 1 (0) ; RNA, Messenger (0) ; Receptors, GABA-B (0) ; Baclofen (1134-47-0) ; gamma-Aminobutyric Acid (56-12-2)

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