title: Cholecystokinin-8 inhibits methamphetamine-induced neurotoxicity via an anti-oxidative stress pathway.
abstract: As a powerful addictive psychostimulant drug, coupled with its neurotoxicity, methamphetamine (METH) abuse may lead to long-lasting abnormalities in brain structure and function. We found that pretreatment of cholecystokinin-8 (CCK-8) inhibited METH-induced brain cellular dopaminergic (DA) damage in the striatum and substantia nigra, and related behavioural deficits and hyperthermia. However, the mechanism of CCK-8 action on METH-induced toxicity is not clear. The aim of this study was to explore whether the possible protective effect of CCK-8 on METH-induced neurotoxicity involved anti-oxidative stress mechanisms. The subtypes of CCK receptors mediating the regulatory action of CCK-8 were also investigated. The present results revealed that CCK-8 dose-dependently inhibited METH-induced cytotoxic effect by activating the CCK2 receptor subtype in PC12 cells and CCK2 receptor stable transfected-HEK293 cells. Pre-treatment of CCK-8 before METH stimulation significantly attenuated the generation of reactive oxygen species and NADPH oxidase activation in PC12 cells. In conclusion, our study demonstrated a protective effect of CCK-8 on METH-induced neurotoxicity in vitro and suggested that a possible mechanism of this action was dependent on the activation of the CCK2 receptor to reduce the neurotoxicity and oxidative stress induced by METH stimulation.
authors: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China.
authors: Di
authors: D
authors: Wen
authors: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China.
authors: Meiling
authors: M
authors: An
authors: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China.
authors: Hongyan
authors: H
authors: Gou
authors: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China.
authors: Xia
authors: X
authors: Liu
authors: The 8th Brigade of General Division of Criminal Investigation, Beijing Municipal Public Security Bureau, Beijing 100006, PR China.
authors: Li
authors: L
authors: Liu
authors: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China. Electronic address: chunlingma@126.com.
authors: Chunling
authors: C
authors: Ma
authors: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China. Electronic address: hbydbincong@126.com.
authors: Bin
authors: B
authors: Cong
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D002766:Cholecystokinin / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D043887:Receptor, Cholecystokinin B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection
chemical_list: C414047:CCL28 protein, human; D000697:Central Nervous System Stimulants; D019742:Chemokines, CC; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D043887:Receptor, Cholecystokinin B; C410885:cholecystokinin 8; D008694:Methamphetamine; D008315:Malondialdehyde; D002766:Cholecystokinin; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1
keywords: CCK-8; CCK2 receptor; Cytotoxicity; Methamphetamine; Oxidative stress