title: Chronic exposure to morphine decreases the expression of EAAT3 via opioid receptors in hippocampal neurons.
abstract: Alterations in glutamate transporter expression are closely related to opiate addition behavior, but the role of opioid receptors is unclear. In this study, we used primary cultures of hippocampal neurons from neonatal rats to study the effects of chronic exposure to morphine on excitatory amino acid transporter 3 (EAAT3) expression and the roles of µ opioid receptor (MOR), δ opioid receptor (DOR), and κ opioid receptor (KOR) in the morphine-dependent alterations in EAAT3 expression. The results showed that the EAAT3 protein and mRNA expression levels decreased significantly after chronic exposure to morphine (10μmol/L) for 48h, whereas the concentration of extracellular glutamate increased. In addition, we found that both the MOR inhibitor CTOP and the DOR inhibitor naltrindole could reverse the decreased expression of EAAT3 after exposure to morphine, whereas the MOR activator DAMGO and the DOR activator DPDPE significantly decreased EAAT3 expression. The KOR inhibitor had no effect on the expression of EAAT3, whereas its activator increased EAAT3 expression. These results suggest that the down-regulation of morphine-dependent EAAT3 expression in primary rat hippocampal cultures may be mediated by MOR and DOR and that KOR may not contribute significantly to this effect.
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China.
authors.forename: Dexiong
authors.initials: D
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China.
authors.forename: Ganglan
authors.initials: G
authors.lastname: Fu
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China. Electronic address: xafony@qq.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China. Electronic address: caofox5188@126.com.
authors.forename: Minghui
authors.initials: M
authors.lastname: Cao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011957:Receptors, Opioid / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
chemical_list: D050580:Excitatory Amino Acid Transporter 3; D009292:Narcotic Antagonists; D009294:Narcotics; D012333:RNA, Messenger; D011957:Receptors, Opioid; C493398:Slc1a1 protein, rat; D018698:Glutamic Acid; D009020:Morphine
keywords: Addiction behavior; Excitatory amino acid transporter 3; Hippocampal neuron; Morphine; Opioid receptor