title: Effects of topiramate on oral dyskinesia induced by reserpine.
abstract: Recently, we have described the antidyskinetic property of the GABA mimetic drug valproic acid on reserpine-induced oral dyskinesia, an animal model that has been related to tardive as well as acute dyskinesias, which are associated with important neuropathologies. The present study investigates the effects of different doses of the GABA mimetic anticonvulsant topiramate on the manifestation of reserpine-induced orofacial dyskinesia. Female EPM-M1 mice received two injections of control solution or of 0.5 mg/kg reserpine separated by 48 h. Twenty-four hours after the second reserpine or control solution injection, animals were acutely treated with control solution or topiramate (1, 3, 10 or 30 mg/kg) and were observed for quantification of oral dyskinesia or general activity in an open-field. In order to verify the effects of topiramate per se on oral dyskinesia or general activity, female EPM-M1 mice were acutely treated with control solution or 1, 3, 10 or 30 mg/kg topiramate and observed for quantification of oral dyskinesia and general activity. The highest dose of topiramate completely abolished the manifestation of reserpine-induced oral dyskinesia whereas the doses of 3 and 10 mg/kg significantly attenuated it. None of the doses of the anticonvulsant modified spontaneous locomotion frequency or oral movements, whereas spontaneous rearing frequency was decreased by 3, 10 and 30 mg/kg topiramate. The highest dose of topiramate did not modify general activity in reserpine-treated mice. These results support the potential therapeutic use of topiramate in the treatment of oral dyskinesias.
authors.affiliation: Department of Pharmacology, Escola Paulista de Medicina/UNIFESP, São Paulo, Brazil.
authors.forename: Nilza P
authors.initials: NP
authors.lastname: Araujo
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Abílio
authors.forename: Regina H
authors.initials: RH
authors.lastname: Silva
authors.forename: Renata C
authors.initials: RC
authors.lastname: Pereira
authors.forename: Rita C
authors.initials: RC
authors.lastname: Carvalho
authors.forename: Carla
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Rogério G
authors.initials: RG
authors.lastname: Bellot
authors.forename: Juliana P M V
authors.initials: JP
authors.lastname: Castro
authors.forename: Daniela F
authors.initials: DF
authors.lastname: Fukushiro
authors.forename: Marcelo S D
authors.initials: MS
authors.lastname: Rodrigues
authors.forename: Cibele C
authors.initials: CC
authors.lastname: Chinen
authors.forename: Roberto
authors.initials: R
authors.lastname: Frussa-Filho
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008124:Locomotion / Q000187:drug effects; D008409:Mastication / Q000187:drug effects; D008425:Maternal Behavior / Q000187:drug effects; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012110:Reserpine / Q000633:toxicity*; D000077236:Topiramate
chemical_list: D018759:Adrenergic Uptake Inhibitors; D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose; D012110:Reserpine