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However, chronic treatment with benzodiazepines is known to induce dependence, which is considered related to neuroplastic changes in the mesolimbic system. This study investigated the involvement of K\n                    <jats:sup>+<\/jats:sup>\n                    \u2010Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    co\u2010transporter 2 (KCC2) in the sensitization to morphine\u2010induced hyperlocomotion after chronic treatment with zolpidem [a selective agonist of \u03b3\u2010aminobutyric acid A\u2010type receptor (GABA\n                    <jats:sub>A<\/jats:sub>\n                    R) \u03b11 subunit]. In this study, chronic treatment with zolpidem enhanced morphine\u2010induced hyperlocomotion, which is accompanied by the up\u2010regulation of KCC2 in the limbic forebrain. We also found that chronic treatment with zolpidem induced the down\u2010regulation of protein phosphatase\u20101 (PP\u20101) as well as the up\u2010regulation of phosphorylated protein kinase C \u03b3 (\n                    <jats:styled-content style=\"fixed-case\">pPKC<\/jats:styled-content>\n                    \u03b3). Furthermore, PP\u20101 directly associated with KCC2 and\n                    <jats:styled-content style=\"fixed-case\">pPKC<\/jats:styled-content>\n                    \u03b3, whereas\n                    <jats:styled-content style=\"fixed-case\">pPKC<\/jats:styled-content>\n                    \u03b3 did not associate with KCC2. On the other hand, pre\u2010treatment with furosemide (a KCC2 inhibitor) suppressed the enhancing effects of zolpidem on morphine\u2010induced hyperlocomotion. These results suggest that the mesolimbic dopaminergic system could be amenable to neuroplastic change through a\n                    <jats:styled-content style=\"fixed-case\">pPKC<\/jats:styled-content>\n                    \u03b3\u2010PP\u20101\u2010KCC2 pathway by chronic treatment with zolpidem.\n                  <\/jats:p>","DOI":"10.1111\/jnc.12258","type":"journal-article","created":{"date-parts":[[2013,4,8]],"date-time":"2013-04-08T22:32:26Z","timestamp":1365460346000},"page":"747-755","source":"Crossref","is-referenced-by-count":14,"title":["Involvement of the K\n                    <sup>+<\/sup>\n                    \u2010Cl\n                    <sup>\u2212<\/sup>\n                    co\u2010transporter\n                    <scp>KCC<\/scp>\n                    2 in the sensitization to morphine\u2010induced hyperlocomotion under chronic treatment with zolpidem in the mesolimbic system"],"prefix":"10.1111","volume":"125","author":[{"given":"Masahiro","family":"Shibasaki","sequence":"first","affiliation":[{"name":"Department of Toxicology Hoshi University School of Pharmacy and Pharmaceutical Sciences Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Masukawa","sequence":"additional","affiliation":[{"name":"Department of Toxicology Hoshi University School of Pharmacy and Pharmaceutical Sciences Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Toxicology Hoshi University School of Pharmacy and Pharmaceutical Sciences Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Department of Toxicology Hoshi University School of Pharmacy and Pharmaceutical Sciences Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohisa","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Toxicology Hoshi University School of Pharmacy and Pharmaceutical Sciences Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Toxicology Hoshi University School of Pharmacy and Pharmaceutical Sciences Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,4,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2007.03.028"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn920"},{"key":"e_1_2_7_4_1","first-page":"18","article-title":"Detection of benzodiazepine abuse in opiate addicts","volume":"91","author":"Browne R.","year":"1998","journal-title":"Ir. 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