Effects of acute and chronic quercetin administration on methylphenidate-induced hyperlocomotion and oxidative stress.

Autor: Kanazawa LK; Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil., Vecchia DD; Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil., Wendler EM; Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil., Hocayen PA; Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil., Beirão PS Jr; Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil., de Mélo ML; Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil., Dos Reis Lívero FA; Laboratory of Pharmacology and Metabolism, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil., Corso CR; Laboratory of Pharmacology and Metabolism, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil., Stipp MC; Laboratory of Pharmacology and Metabolism, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil., Acco A; Laboratory of Pharmacology and Metabolism, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, Curitiba, PR 81540-990, Brazil., Andreatini R; 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.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2017 Feb 15; Vol. 171, pp. 1-8. Date of Electronic Publication: 2017 Jan 16.
DOI: 10.1016/j.lfs.2017.01.007
Abstrakt: Aims: 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.
Main 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.
Key Findings: 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.
Significance: 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.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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