title: Glutamate transporter type 3 participates in maintaining morphine-induced conditioned place preference.
abstract: Glutamate transporters (EAAT) have been implicated in the drug addiction behavior. We determined whether EAAT type 3 (EAAT3) played a role in morphine addiction. Six- to eight-week-old EAAT3 knockout (EAAT3-/-) mice and their wild-type littermates received 3 intraperitoneal injections of 10mg/kg morphine, each on an alternative day, to induce conditioned place preference (CPP). Two days after the place preference returned to baseline, mice received 2.5mg/kg morphine to induce reinstatement. Some mice received intraperitoneal injection of 4mg/kg riluzole, an EAAT activator, 30min before morphine or saline injection. Hippocampus, medial prefrontal cortex, nucleus accumbens and ventral tegmental area were harvested for Western analysis 24h after the last dose of morphine was injected. Morphine induced CPP in wild-type and EAAT3-/-mice. Gender is not a statistically significant factor to influence this behavior. This conditioned behavior extinguished after morphine administration was stopped for 8-9days in wild-type mice, while this extinction occurred 6days after discontinuation of morphine injection in EAAT3-/-mice. A small dose of morphine similarly reinstated the conditioned behavior in the wild-type and EAAT3-/-mice. Riluzole abolished morphine-induced CPP during the initial place preference. Morphine increased EAAT3 expression in the plasma membrane of medial prefrontal cortex, nucleus accumbens and ventral tegmental area but did not affect EAAT3 expression in the hippocampus. These results suggest that EAAT3 delays the extinction of morphine-induced CPP. EAAT activation may prevent the formation of morphine-induced CPP.
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States; Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States; Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jiangjiang
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States. Electronic address: zz3c@virginia.edu.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics / Q000378:metabolism*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism; D009294:Narcotics / Q000494:pharmacology*; D019782:Riluzole / Q000494:pharmacology; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D050580:Excitatory Amino Acid Transporter 3; D009294:Narcotics; C493399:Slc1a1 protein, mouse; D009020:Morphine; D019782:Riluzole
keywords: conditioned place preference; glutamate transporter; mice; morphine