UM
Lithium normalizes amphetamine-induced changes in striatal FoxO1 phosphorylation and behaviors in rats
Zheng W.1; Zeng Z.1; Bhardwaj S.K.3; Jamali S.3; Srivastava L.K.3
2013-07-10
Source PublicationNeuroReport
ISSN09594965 1473558X
Volume24Issue:10Pages:560-565
AbstractAdministration of the psychostimulant drug amphetamine (AMPH) to animals causes hyperactivity and deficit in prepulse inhibition (PPI) of startle, behaviors that are often observed in neuropsychiatric disorders such as schizophrenia and bipolar disorder. Enhanced central dopamine (DA) transmission is believed to mediate AMPH-induced behavioral alterations. Lithium, a drug used primarily in the treatment of bipolar disorder, is reported to interact with the DA system and antagonize some DA-related behaviors. Here, we provide evidence that AMPH and lithium reciprocally regulate the activity of the transcription factor forkhead box, class O1 (FoxO1), a downstream target of Akt. Administration of d-AMPH (3 mg/kg, intraperitoneally) to Sprague-Dawley rats resulted in a concomitant decrease in levels of phosphorylated (p) Akt as well as p-FoxO1 in the striatum, whereas lithium chloride (LiCl,100 mg/kg, intraperitoneally) exerted the opposite effect, that is, it increased levels of p-Akt and p-FoxO1. Pretreatment of animals with lithium prevented an AMPH-induced decrease in striatal p-Akt and p-FoxO1 levels. Pretreatment of animals with lithium also attenuated AMPH-induced locomotor activity and decreased prepulse inhibition. These in-vivo data suggest that the Akt-FoxO1 pathway may be a common target for the action of dopaminergic and antidopaminergic drugs, and its modulation may be relevant to the treatment of neuropsychiatric disorders. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
KeywordAkt amphetamine behavior bipolar disorder class O1 Forkhead box lithium prepulse inhibition schizophrenia striatum
DOI10.1097/WNR.0b013e3283623725
URLView the original
Language英語
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Cited Times [WOS]:12   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.School of Pharmaceutical Sciences
2.Zhongshan Ophthalmic Center
3.McGill University, Douglas Mental Health University Institute
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Zheng W.,Zeng Z.,Bhardwaj S.K.,et al. Lithium normalizes amphetamine-induced changes in striatal FoxO1 phosphorylation and behaviors in rats[J]. NeuroReport,2013,24(10):560-565.
APA Zheng W.,Zeng Z.,Bhardwaj S.K.,Jamali S.,&Srivastava L.K..(2013).Lithium normalizes amphetamine-induced changes in striatal FoxO1 phosphorylation and behaviors in rats.NeuroReport,24(10),560-565.
MLA Zheng W.,et al."Lithium normalizes amphetamine-induced changes in striatal FoxO1 phosphorylation and behaviors in rats".NeuroReport 24.10(2013):560-565.
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