title: Protective effects of cholecystokinin-8 on methamphetamine-induced behavioral changes and dopaminergic neurodegeneration in mice.
abstract: We investigated whether pretreatment with the neuropeptide cholecystokinin-8 affected methamphetamine (METH)-induced behavioral changes and dopaminergic neurodegeneration in male C57/BL6 mice. CCK-8 pretreatment alone had no effect on locomotion and stereotypic behavior and could not induce behavioral sensitization; however, it attenuated, in a dose-dependent manner, hyperlocomotion and behavioral sensitization induced by a low dose of METH (1mg/kg). CCK-8 attenuated METH-induced stereotypic behavior at a dose of 3mg/kg but not at 10mg/kg. CCK-8 pretreatment attenuated METH (10mg/kg)-induced hyperthermia, the decrease of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the striatum, and TH in the substantia nigra. CCK-8 alone had no effect on rectal temperature, TH and DAT expression in the nigrostriatal region. In conclusion, our study demonstrated that pretreatment with CCK-8 inhibited changes typically induced by repeated exposure to METH, such as hyperlocomotion, behavioral sensitization, stereotypic behavior, and dopaminergic neurotoxicity. These findings make CCK-8 a potential therapeutic agent for the treatment of multiple symptoms associated with METH abuse.
authors: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, China.
authors: Hongyan
authors: H
authors: Gou
authors: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, China.
authors: Di
authors: D
authors: Wen
authors: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, 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, Shijiazhuang 050017, China.
authors: Ming
authors: M
authors: Li
authors: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, China.
authors: Yingmin
authors: Y
authors: Li
authors: The 8th Brigade of General Division of Criminal Investigation, Beijing Municipal Public Security Bureau, Beijing 100006, China.
authors: Wenfang
authors: W
authors: Zhang
authors: The 8th Brigade of General Division of Criminal Investigation, Beijing Municipal Public Security Bureau, Beijing 100006, China.
authors: Li
authors: L
authors: Liu
authors: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, China. Electronic address: hbydbincong@126.com.
authors: Bin
authors: B
authors: Cong
mesh_terms: D019969:Amphetamine-Related Disorders / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002766:Cholecystokinin / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D015259:Dopamine Agents / Q000633:toxicity*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011897:Random Allocation; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C410885:cholecystokinin 8; D008694:Methamphetamine; D002766:Cholecystokinin; D014446:Tyrosine 3-Monooxygenase
keywords: CCK-8; Methamphetamine; Neurodegeneration; Sensitization; Stereotypic behavior