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.
Frey, H. H., Jung, S., & Scherkl, R. (1991). Monoamine turnover in the brain of mice during development of tolerance to the anticonvulsant effect of clonazepam. Epilepsy Research, 8(3), 190–196. https://doi.org/10.1016/0920-1211(91)90063-L