Differential expression of GABA(A) receptor subunit mRNAs and ligand binding sites in rat brain following phencyclidine administration

Shuzo Abe, Toshihito Suzuki, Takehiko Ito, Atsuomi Baba, Takafumi Hori, Hirofumi Kurita, Mika Yamaguchi, Hiroyasu Shiraishi

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Recent biochemical observations have suggested the abnormalities in the γ-amino-butyric acid (GABA)ergic system in schizophrenic brains. In the present study, we investigated the subunits gene expressions and ligand binding of the GABA(A) receptor following acute and chronic administration of phencyclidine (PCP), which induces schizophrenia-like symptoms, in rats using in situ hybridization and in vitro quantitative autoradiography. PCP i.p. administration at a daily dose of 7.5 mg/kg resulted in a significant decrease in expression of α1 subunit mRNA in cerebral cortices (cingulate (-13%) and temporal cortex (-6%)) and hippocampal formation (CA1 (-11%), CA2 (-10%), CA3 (-11%) and dentate gyrus (-12%)) 1 h after a single treatment. In the repeated PCP administrations for 14 days, the expression of β2 mRNA in the cerebellum (-10%) and of β3 mRNA in the cerebral cortices (cingulate (-12%), parietal (-16%) and temporal cortex (-16%), caudate putamen (-18%), inferior colliculus (-18%), and cerebel-lum (-15%) were significantly decreased. In addition, [35S]t-butylbicyclophosphorothionate (TBPS) binding was also reduced in layer IV of the frontoparietal cortex (-14%), inferior colliculus (-17%), and cerebellum (-12%) following chronic PCP treatment, while no changes were observed following acute PCP treatment. These results indicate that single and repeated administrations of PCP independently regulate the expression of GABA(A)/benzodiazepine (BZD) receptor subunits mRNA and its receptor binding in the brain. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalSynapse
Volume38
Issue number1
DOIs
Publication statusPublished - 2000

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Phencyclidine
GABA-A Receptors
Binding Sites
Ligands
Inferior Colliculi
Messenger RNA
Brain
Temporal Lobe
Cerebral Cortex
Cerebellum
Parietal Lobe
Butyric Acid
Putamen
Gyrus Cinguli
Dentate Gyrus
Autoradiography
gamma-Aminobutyric Acid
In Situ Hybridization
Hippocampus
Schizophrenia

Keywords

  • Autoradiography
  • GABA
  • In situ hybridization
  • NMDA antagonist
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Differential expression of GABA(A) receptor subunit mRNAs and ligand binding sites in rat brain following phencyclidine administration. / Abe, Shuzo; Suzuki, Toshihito; Ito, Takehiko; Baba, Atsuomi; Hori, Takafumi; Kurita, Hirofumi; Yamaguchi, Mika; Shiraishi, Hiroyasu.

In: Synapse, Vol. 38, No. 1, 2000, p. 51-60.

Research output: Contribution to journalArticle

Abe, Shuzo ; Suzuki, Toshihito ; Ito, Takehiko ; Baba, Atsuomi ; Hori, Takafumi ; Kurita, Hirofumi ; Yamaguchi, Mika ; Shiraishi, Hiroyasu. / Differential expression of GABA(A) receptor subunit mRNAs and ligand binding sites in rat brain following phencyclidine administration. In: Synapse. 2000 ; Vol. 38, No. 1. pp. 51-60.
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AB - Recent biochemical observations have suggested the abnormalities in the γ-amino-butyric acid (GABA)ergic system in schizophrenic brains. In the present study, we investigated the subunits gene expressions and ligand binding of the GABA(A) receptor following acute and chronic administration of phencyclidine (PCP), which induces schizophrenia-like symptoms, in rats using in situ hybridization and in vitro quantitative autoradiography. PCP i.p. administration at a daily dose of 7.5 mg/kg resulted in a significant decrease in expression of α1 subunit mRNA in cerebral cortices (cingulate (-13%) and temporal cortex (-6%)) and hippocampal formation (CA1 (-11%), CA2 (-10%), CA3 (-11%) and dentate gyrus (-12%)) 1 h after a single treatment. In the repeated PCP administrations for 14 days, the expression of β2 mRNA in the cerebellum (-10%) and of β3 mRNA in the cerebral cortices (cingulate (-12%), parietal (-16%) and temporal cortex (-16%), caudate putamen (-18%), inferior colliculus (-18%), and cerebel-lum (-15%) were significantly decreased. In addition, [35S]t-butylbicyclophosphorothionate (TBPS) binding was also reduced in layer IV of the frontoparietal cortex (-14%), inferior colliculus (-17%), and cerebellum (-12%) following chronic PCP treatment, while no changes were observed following acute PCP treatment. These results indicate that single and repeated administrations of PCP independently regulate the expression of GABA(A)/benzodiazepine (BZD) receptor subunits mRNA and its receptor binding in the brain. (C) 2000 Wiley-Liss, Inc.

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