Development of tolerance to anxiolytic effects of chlordiazepoxide in elevated plus-maze test and decrease of GABAA receptors

S. Ishihara, M. Hiramatsu, T. Kameyama, T. Nabeshima

研究成果: Article査読

15 被引用数 (Scopus)

抄録

Repeated administration of benzodiazepines has been reported to produce tolerance in animals and humans. Using an elevated plus-maze test and an autoradiographic technique, we investigated whether repeated administration of chlordiazepoxide produced tolerance to its anxiolytic effects, and whether such repeated administration altered benzodiazepine and GABAA receptors. Tolerance to the anxiolytic effect of chlordiazepoxide was produced when it was administered at a dose of 30 mg/kg (i.p.) once a day for 10 and 14 days. In the quantitative autoradiographical study, although repeated chlordiazepoxide treatment had no effect on [3H]flunitrazepam and [3H]Ro 15-4513 binding to benzodiazepine receptors, such treatment reduced [3H]muscimol binding to GABAA receptors in the cortex, caudate putamen, and hippocampus. These results suggest firstly, the production of tolerance to the anxiolytic effects of chlordiazepoxide, and, secondly, that this tolerance may be due to the down-regulation of GABAA receptors, but not of benzodiazepine receptors.

本文言語English
ページ(範囲)27-37
ページ数11
ジャーナルJournal of Neural Transmission
91
1
DOI
出版ステータスPublished - 01-02-1993
外部発表はい

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

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