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.
Keywords:
CCK-8; Methamphetamine; Neurodegeneration; Sensitization; Stereotypic behavior.
Copyright © 2015 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amphetamine-Related Disorders / drug therapy
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Amphetamine-Related Disorders / pathology
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Amphetamine-Related Disorders / physiopathology
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Animals
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Body Temperature / drug effects
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Cholecystokinin / pharmacology*
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Corpus Striatum / drug effects
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Corpus Striatum / pathology
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Corpus Striatum / physiopathology
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Dopamine Agents / toxicity*
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Dopamine Plasma Membrane Transport Proteins / metabolism
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Dopaminergic Neurons / drug effects*
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Dopaminergic Neurons / pathology
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Dopaminergic Neurons / physiology
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Dose-Response Relationship, Drug
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Dyskinesia, Drug-Induced / drug therapy
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Dyskinesia, Drug-Induced / physiopathology
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Male
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Methamphetamine / toxicity*
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Mice, Inbred C57BL
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Motor Activity / drug effects
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Motor Activity / physiology
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Neurodegenerative Diseases / chemically induced
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Neurodegenerative Diseases / drug therapy*
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Neurodegenerative Diseases / pathology
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Neurodegenerative Diseases / physiopathology
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Neuroprotective Agents / pharmacology*
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Peptide Fragments / pharmacology*
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Random Allocation
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Stereotyped Behavior / drug effects
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Stereotyped Behavior / physiology
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Substantia Nigra / drug effects
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Substantia Nigra / pathology
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Substantia Nigra / physiopathology
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Tyrosine 3-Monooxygenase / metabolism
Substances
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Dopamine Agents
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Dopamine Plasma Membrane Transport Proteins
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Neuroprotective Agents
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Peptide Fragments
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cholecystokinin 8
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Methamphetamine
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Cholecystokinin
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Tyrosine 3-Monooxygenase