Monoamine turnover in the brain of mice during development of tolerance to the anticonvulsant effect of clonazepam.
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.
Frey
H H
HH
Department of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, F.R.G.
Jung
S
S
Scherkl
R
R
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D002998:Clonazepam / Q000494:pharmacology* / Q000627:therapeutic use; D004361:Drug Tolerance; D004827:Epilepsy / Q000188:drug therapy; D008297:Male; D051379:Mice
D015306:Biogenic Monoamines; D002998:Clonazepam