Monoamine turnover in the brain of mice during development of tolerance to the anticonvulsant effect of clonazepam |
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Authors: | H H Frey S Jung R Scherkl |
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Affiliation: | Department of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universit?t Berlin, F.R.G. |
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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. |
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