Epileptogenesis and Enhanced Prepulse Inhibition in GABAB1-Deficient Mice

doi:10.1006/mcne.2001.0995

Molecular and Cellular Neuroscience

Volume 17, Issue 6, June 2001, Pages 1059-1070

https://doi.org/10.1006/mcne.2001.0995 Get rights and content

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.

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Citation Excerpt :
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¹: To whom correspondence and reprint requests should be addressed. E-mail: [email protected].

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Regular ArticleEpileptogenesis and Enhanced Prepulse Inhibition in GABAB1-Deficient Mice

Abstract

Curr. Opin. Neurobiol.

Trends Pharmacol. Sci.

Mol. Cell. Neurosci.

J. Biol. Chem.

Pharmacol. Ther

Neuron.

Mol. Cell. Neurosci.

Behav. Neural. Biol.

Int. Rev. Neurobiol.

J. Biol. Chem.

Biol. Psychiatr.

Behav. Brain Res.

Neuroscience

Mol. Cell. Neurosci.

Anticonvulsant-like actions of baclofen in the rat hippocampal slice

Br. J. Pharmacol.

Spatial distribution of GABABR1 receptor mRNA and binding sites in rat brain

J. Comp. Neurol.

Gamma-aminobutyric acid(B) receptors: First of the functional metabotropic heterodimers

J. Pharmacol. Exp. Ther.

Prestimulus effects on human startle reflex in normals and schizophrenics

Psychophysiology

Sensorimotor gating and schizophrenia. Human and animal studies

Arch. Gen. Psychiatr.

Paired-pulse depression of monosynaptic GABA-mediated inhibitory postsynaptic responses in rat hippocampus

J. Physiol.

Regular Article
Epileptogenesis and Enhanced Prepulse Inhibition in GABA_B1-Deficient Mice

Spatial distribution of GABA_BR1 receptor mRNA and binding sites in rat brain