title: Effects of the altered activity of δ-opioid receptor on the expression of glutamate transporter type 3 induced by chronic exposure to morphine.
abstract: Altered δ-opioid receptor (DOR) activity can affect the activity and function of excitatory amino acid transporter 3 (EAAT3), but the effects of DOR on EAAT3 expression in morphine relapse remain unknown. In this study, a C6δ cell line and SD rats in a conditioned place preference (CPP) reinstatement model were used. Here, we show that EAAT3 protein levels in C6δ cells decreased significantly after chronic exposure to morphine (10 μM) for 48 h and returned to normal 12 h after drug withdrawal. When C6δ cells were re-exposed to 5 μM morphine for 4 h, EAAT3 protein levels again decreased significantly. The selective μ opioid receptor (MOR) specific agonist DAMGO had a similar effect as morphine, and CTOP, a specific MOR blocker, reversed the declined expression of EAAT3 protein triggered by morphine exposure. The selective DOR agonist [d-pen2, 5] enkephalin (DPDPE) significantly increased EAAT3 expression in C6δ cells and even reversed the decreased EAAT3 expression caused by chronic morphine exposure. The non specific antagonist naloxone, but not the DOR inhibitor Naltrindole (NTI), reversed the decreased EAAT3 expression in C6δ cells caused by chronic morphine exposure. In vivo, EAAT3 levels in the prefrontal cortex of rats with morphine-induced CPP reinstatement significantly decreased. Naloxone completely suppressed reinstatement and reversed the decrease in EAAT3 expression induced by morphine re-exposure. In contrast, NTI only weakened CPP reinstatement and exerted no influence on EAAT3 expression. These findings suggest that DOR can affect the expression of EAAT3. However, the morphine-induced down-regulation of EAAT3 in C6δ cells and in the prefrontal cortex of rats may not be mediated by DOR.
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Shuxuan
authors.initials: S
authors.lastname: Xia
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Dexiong
authors.initials: D
authors.lastname: Cao
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Yanni
authors.initials: Y
authors.lastname: Fu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liang
authors.forename: Minghui
authors.initials: M
authors.lastname: Cao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003216:Conditioning, Operant / Q000187:drug effects; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics / Q000378:metabolism*; D005108:Extinction, Psychological / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005910:Glioma / Q000473:pathology; D009022:Morphine Derivatives / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000235:genetics / Q000378:metabolism*; D012201:Reward; D013997:Time Factors; D014162:Transfection
chemical_list: D050580:Excitatory Amino Acid Transporter 3; D009022:Morphine Derivatives; D009294:Narcotics; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; C493398:Slc1a1 protein, rat
keywords: Addiction; C6 cells; Conditioned place preference; Excitatory amino acid transporter; Morphine; δ-opioid receptor