title: Valproate Inhibits Methamphetamine Induced Hyperactivity via Glycogen Synthase Kinase 3β Signaling in the Nucleus Accumbens Core.
abstract: Valproate (VPA) has recently been shown to influence the behavioral effects of psycho-stimulants. Although glycogen synthase kinase 3β (GSK3β) signaling in the nucleus accumbens (NAc) plays a key role in mediating dopamine (DA)-dependent behaviors, there is less direct evidence that how VPA acts on the GSK3β signaling in the functionally distinct sub-regions of the NAc, the NAc core (NAcC) and the NAc shell (NAcSh), during psycho-stimulant-induced hyperactivity. In the present study, we applied locomotion test after acute methamphetamine (MA) (2 mg/kg) injection to identify the locomotor activity of rats received repeated VPA (300 mg/kg) pretreatment. We next measured phosphor-GSK3β at serine 9 and total GSK3β levels in NAcC and NAcSh respectively to determine the relationship between the effect of VPA on MA-induced hyperlocomotor and changes in GSK3β activity. We further investigated whether microinjection of VPA (300 μg/0.5 μl/side, once daily for 7 consecutive days) into NAcC or NAcSh could affect hyperactivity induced by MA. Our data indicated that repeated VPA treatment attenuated MA-induced hyperlocomotor, and the effect was associated with decreased levels of phosphorylated GSK3β at Ser 9 in the NAcC. Moreover, repeated bilateral intra-NAcC, but not intra-NAcSh VPA treatment, significantly attenuated MA-induced hyperactivity. Our results suggested that GSK3β activity in NAcC contributes to the inhibitory effects of VPA on MA-induced hyperactivity.
authors.affiliation: Department of Forensic Medicine, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, PR China; Xi'an Mental Health Center, Xi'an, Shaanxi, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xing
authors.affiliation: Xi'an Mental Health Center, Xi'an, Shaanxi, PR China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Liang
authors.affiliation: Department of Forensic Medicine, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Forensic Medicine, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, PR China; Department of Pathophysiology, School of basic Medicine Sciences, Xi'an Medical University, Xi'an, Shaanxi, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Forensic Medicine, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chu
authors.affiliation: Department of Forensic Medicine, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, PR China.
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Dang
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000037:antagonists & inhibitors; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006948:Hyperkinesis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D012694:Serine; D014635:Valproic Acid; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3