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Chronic pentobarbital administration alters γ‐aminobutyric acid A receptor α 6 ‐subunit mRNA levels and diazepam‐insensitive [ 3 H]Ro15‐4513 binding
Author(s) -
Ito Takehiko,
Suzuki Toshihito,
Wellman Susan E.,
Ho Ing K.
Publication year - 1996
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199602)22:2<106::aid-syn3>3.0.co;2-h
Subject(s) - pentobarbital , receptor , medicine , gabaa receptor , endocrinology , protein subunit , diazepam , chemistry , pharmacology , alpha (finance) , agonist , in situ hybridization , benzodiazepine , messenger rna , biology , biochemistry , gene , construct validity , nursing , patient satisfaction
In order to study the chronic effects of pentobarbital, a positive GABA A receptor modulator, on the inverse agonist binding of the benzodiazepine site, binding of[ 3 H]Ro15‐4513 and levels of GABA A receptorα 6 ‐subunit mRNA were investigated in the brains ofpentobarbital‐tolerant/dependent animals, using receptor autoradiography and in situhybridization histochemistry in consecutive brain sections. Pentobarbital was administered torats either 60 mg/kg, i.p., once, for acute treatment, or 300 μg/10μl/h i.c.v.continuously for 6 days via osmotic minipumps to render rats tolerant to pentobarbital. Ratsassigned to the dependent group were sacrificed 24 h after discontinuance of pentobarbitalinfusion, while those assigned to the tolerant group were sacrificed at the end of infusion. Theα 6 subunit mRNA was increased in the tolerant group only.Diazepam‐insensitive [ 3 H]Ro15‐4513 binding was increased in the cerebellargranule layer of pentobarbital‐tolerant and ‐dependent rats. No alterations in these parameterswere observed in acutely treated animals. These data suggest that chronic pentobarbitaltreatment induced expression of α 6 ‐subunit mRNA. This was in contrast toα 1 ‐ and γ 2 ‐subunit mRNA, which in tolerant animals areunchanged, but for which withdrawal triggers a surge in levels. Because theα 6 ‐subunit is a major component of the diazepam‐insensitive[ 3 H]Ro15‐4513 binding site, the increased diazepam‐insensitive[ 3 H]Ro15‐4513 binding implied de novo synthesis of the receptor subunitprotein. © 1996 Wiley‐Liss, Inc.