title: Glycogen synthase kinase 3β in the nucleus accumbens core is critical for methamphetamine-induced behavioral sensitization.
abstract: As a ubiquitous serine/threonine protein kinase, glycogen synthase kinase 3β (GSK-3β) has been considered to be important in the synaptic plasticity that underlies dopamine-related behaviors and diseases. We recently found that GSK-3β activity in the nucleus accumbens (NAc) core is critically involved in cocaine-induced behavioral sensitization. The present study further explored the association between the changes in GSK-3β activity in the NAc and the chronic administration of methamphetamine. We also examined whether blocking GSK-3β activity in the NAc could alter the initiation and expression of methamphetamine (1 mg/kg, i.p.)-induced locomotor sensitization in rats using systemic administration of lithium chloride (LiCl, 100 mg/kg, i.p) and brain region-specific administration of the GSK-3β inhibitor SB216763 (1 ng/side). We found that GSK-3β activity increased in the NAc core, but not NAc shell, after chronic methamphetamine administration. The initiation and expression of methamphetamine-induced locomotor sensitization was attenuated by systemic administration of LiCl and direct infusion of SB216763 into the NAc core, but not NAc shell. These results indicate that GSK-3β activity in the NAc core mediates the initiation and expression of methamphetamine-induced locomotor sensitization, suggesting that GSK-3β may be a potential target for the treatment of psychostimulant addiction.
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing, China.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Yan-Xue
authors.initials: YX
authors.lastname: Xue
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Zhu
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Li
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhai
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced* / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride