Monoamine turnover in the brain of mice during development of tolerance to the anticonvulsant effect of clonazepam

  • Frey H
  • Jung S
  • Scherkl R
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Abstract

Mice were treated for 14 days with clonazepam, 0.5 mg/kg i.p. twice daily, during which time partial tolerance to the anticonvulsant effect against pentetrazole developed. The development of tolerance was paralleled by a reduced turnover of noradrenaline in the whole brain, and of dopamine in the midbrain. The turnover of 5-HT was increased during the first week of treatment, but decreased thereafter. These changes in monoamine turnover, which are thought to be GABA-mediated, are consistent with an increased seizure susceptibility, and may contribute to the development of tolerance to the anticonvulsant effect of benzodiazepines. © 1991.

Author-supplied keywords

  • Anticonvulsant action
  • Clonazepam
  • Dependence
  • Monoamine turnover
  • Tolerance

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Authors

  • H. H. Frey

  • S. Jung

  • R. Scherkl

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