Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice

Autor: Lu-Tai Tien, Sang Won Park, Richard J. Roman, Xine Shen, Tangeng Ma
Rok vydání: 2011
Předmět:
Dopamine
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Receptors
Opioid
mu
lcsh:Medicine
Pharmacology
Methamphetamine
Mice
chemistry.chemical_compound
Opioid receptor
Pharmacology (medical)
media_common
Mice
Knockout
Central Nervous System Sensitization
Behavior
Animal
General Medicine
GTP-Binding Protein alpha Subunits
Dopamine receptor
addiction
medicine.drug
medicine.drug_class
media_common.quotation_subject
mental disorders
medicine
Animals
Amphetamine
Molecular Biology
Biochemistry
medical
business.industry
Receptors
Dopamine D1
Research
Addiction
lcsh:R
Biochemistry (medical)
Neurotoxicity
Cell Biology
Meth
medicine.disease
Corpus Striatum
Mice
Inbred C57BL
Disease Models
Animal
Gene Expression Regulation
chemistry
μ-opioid receptor
Stereotyped Behavior
business
RGS Proteins
dopamine receptors
Zdroj: Journal of Biomedical Science
Journal of Biomedical Science, Vol 18, Iss 1, p 83 (2011)
ISSN: 1423-0127
Popis: Background Repeated exposure to methamphetamine (METH) can cause not only neurotoxicity but also addiction. Behavioral sensitization is widely used as an animal model for the study of drug addiction. We previously reported that the μ-opioid receptor knockout mice were resistant to METH-induced behavioral sensitization but the mechanism is unknown. Methods The present study determined whether resistance of the μ-opioid receptor (μ-OR) knockout mice to behavioral sensitization is due to differential expression of the stimulatory G protein α subunit (Gαs) or regulators of G-protein signaling (RGS) coupled to the dopamine D1 receptor. Mice received daily intraperitoneal injections of saline or METH (10 mg/kg) for 7 consecutive days to induce sensitization. On day 11(following 4 abstinent days), mice were either given a test dose of METH (10 mg/kg) for behavioral testing or sacrificed for neurochemical assays without additional METH treatment. Results METH challenge-induced stereotyped behaviors were significantly reduced in the μ-opioid receptor knockout mice when compared with those in wild-type mice. Neurochemical assays indicated that there is a decrease in dopamine D1 receptor ligand binding and an increase in the expression of RGS4 mRNA in the striatum of METH-treated μ-opioid receptor knockout mice but not of METH-treated wild-type mice. METH treatment had no effect on the expression of Gαs and RGS2 mRNA in the striatum of either strain of mice. Conclusions These results indicate that down-regulation of the expression of the dopamine D1 receptor and up-regulation of RGS4 mRNA expression in the striatum may contribute to the reduced response to METH-induced stereotypy behavior in μ-opioid receptor knockout mice. Our results highlight the interactions of the μ-opioid receptor system to METH-induced behavioral responses by influencing the expression of RGS of dopamine D1 receptors.
Databáze: OpenAIRE
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