title: Effects of acute and chronic quercetin administration on methylphenidate-induced hyperlocomotion and oxidative stress.
abstract: OBJECTIVE
  Increases in protein kinase C (PKC) and oxidative stress have been related to mania. Drugs with antioxidant effects or inhibitory actions on PKC may have antimanic effects. The flavonoid quercetin has antioxidant and PKC-inhibiting effects that resemble those of lithium, the first-line treatment for mania in bipolar disorder. We hypothesized that quercetin may have antimanic-like effects in an animal model.
  
  
  METHODS
  In the present study, we investigated the effects of acute and chronic treatment with quercetin (2.5, 5, 10, and 40mg/kg, i.p.) in male Swiss mice that were subjected to methylphenidate (5mg/kg, i.p.)-induced hyperlocomotion, an animal model of mania. Lithium (100mg/kg, i.p.) and diazepam (5mg/kg, i.p.) were used as positive and negative controls, respectively. We also evaluated the effects of these treatments on methylphenidate-induced oxidative stress in the brain by measuring reduced glutathione (GSH) and lipid peroxidation (LPO) levels in the prefrontal cortex, hippocampus, and striatum.
  
  
  RESULTS
  Acute and chronic (21-day) treatment with lithium and diazepam reduced methylphenidate-induced hyperlocomotion. Chronic but not acute treatment with quercetin (10 and 40mg/kg) blocked methylphenidate-induced hyperlocomotion. These effects of lithium and quercetin occurred at doses that did not alter spontaneous locomotor activity, whereas diazepam reduced spontaneous locomotor activity. Chronic treatment with lithium and quercetin blocked the methylphenidate-induced increase in LPO levels in the striatum.
  
  
  CONCLUSIONS
  These results suggest that chronic quercetin treatment has antimanic-like and antioxidant effects, thus encouraging further studies of quercetin as a putative new antimanic drug.
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil.
authors.forename: Luiz K S
authors.initials: LK
authors.lastname: Kanazawa
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil.
authors.forename: Débora D
authors.initials: DD
authors.lastname: Vecchia
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil.
authors.forename: Etiéli M
authors.initials: EM
authors.lastname: Wendler
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil.
authors.forename: Palloma de A S
authors.initials: PA
authors.lastname: Hocayen
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil.
authors.forename: Paulo S
authors.initials: PS
authors.lastname: Beirão
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil.
authors.forename: Manuela L
authors.initials: ML
authors.lastname: de Mélo
authors.affiliation: Laboratory of Pharmacology and Metabolism, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil.
authors.forename: Francislaine A
authors.initials: FA
authors.lastname: Dos Reis Lívero
authors.affiliation: Laboratory of Pharmacology and Metabolism, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil.
authors.forename: Claudia Rita
authors.initials: CR
authors.lastname: Corso
authors.affiliation: Laboratory of Pharmacology and Metabolism, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil.
authors.forename: Maria Carolina
authors.initials: MC
authors.lastname: Stipp
authors.affiliation: Laboratory of Pharmacology and Metabolism, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Acco
authors.affiliation: Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil. Electronic address: randreatini@ufpr.br.
authors.forename: Roberto
authors.initials: R
authors.lastname: Andreatini
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008774:Methylphenidate / Q000633:toxicity*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000008:administration & dosage*
chemical_list: D008774:Methylphenidate; D011794:Quercetin
keywords: Bipolar disorder; Hyperlocomotion; Mania; Oxidative stress; Protein kinase C; Quercetin