title: Lithium normalizes amphetamine-induced changes in striatal FoxO1 phosphorylation and behaviors in rats.
abstract: Administration 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.
authors: Department of Neuropharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Wenhua
authors: W
authors: Zheng
authors: Zhiwen
authors: Z
authors: Zeng
authors: Sanjeev K
authors: SK
authors: Bhardwaj
authors: Sara
authors: S
authors: Jamali
authors: Lalit K
authors: LK
authors: Srivastava
mesh_terms: D000661:Amphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D000071161:Forkhead Box Protein O1
chemical_list: D000661:Amphetamine; D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D051858:Forkhead Transcription Factors; D018021:Lithium Chloride; D009419:Nerve Tissue Proteins; D051058:Oncogene Protein v-akt; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1