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

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...

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Published in:Life sciences (1973) Vol. 171; pp. 1 - 8
Main Authors: Kanazawa, Luiz K.S., Vecchia, Débora D., Wendler, Etiéli M., Hocayen, Palloma de A.S., Beirão, Paulo S., de Mélo, Manuela L., dos Reis Lívero, Francislaine A., Corso, Claudia Rita, Stipp, Maria Carolina, Acco, Alexandra, Andreatini, Roberto
Format: Journal Article
Language:English
Published: Netherlands Elsevier Inc 15.02.2017
Elsevier BV
Subjects:
Affective disorders
Animal models
Animals
antioxidant activity
Antioxidants
Behavior, Animal - drug effects
Bipolar disorder
Brain
Brain - drug effects
Diazepam
Dose-Response Relationship, Drug
Glutathione
hippocampus
Hyperlocomotion
Kinases
Lipid peroxidation
Lithium
locomotion
Locomotion - drug effects
Locomotor activity
Male
males
Mania
Manic depression
Methylphenidate
Methylphenidate - toxicity
Mice
Neostriatum
Oxidative stress
Oxidative Stress - drug effects
Peroxidation
Prefrontal cortex
Protein kinase C
Quercetin
Quercetin - administration & dosage
Oxidative stress
BD
Protein kinase C
DTNB
PKC
Bipolar disorder
LPO
PFC
Quercetin
CMC
Mania
Hyperlocomotion
GSH
ISSN:0024-3205, 1879-0631, 1879-0631
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Summary: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. 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. 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. 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.
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ISSN:0024-3205
1879-0631
1879-0631
DOI:10.1016/j.lfs.2017.01.007