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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalJournal of Neural Transmission
Volume91
Issue number1
DOIs
Publication statusPublished - 01-02-1993
Externally publishedYes

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Chlordiazepoxide
Anti-Anxiety Agents
GABA-A Receptors
Flunitrazepam
Muscimol
Putamen
Benzodiazepines
Hippocampus
Down-Regulation

All Science Journal Classification (ASJC) codes

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

Cite this

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abstract = "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.",
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Development of tolerance to anxiolytic effects of chlordiazepoxide in elevated plus-maze test and decrease of GABAA receptors. / Ishihara, S.; Hiramatsu, M.; Kameyama, T.; Nabeshima, Toshitaka.

In: Journal of Neural Transmission, Vol. 91, No. 1, 01.02.1993, p. 27-37.

Research output: Contribution to journalArticle

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