{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:39:58Z","timestamp":1791301198323,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T00:00:00Z","timestamp":1408924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"funder":[{"name":"Grant-in-Aids from the Ministry of Education, Culture, Sports, Science and Technology","award":["23659522"],"award-info":[{"award-number":["23659522"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Developmental disorders including cognitive deficit, hyperkinetic disorder, and autistic behaviors are frequently comorbid in epileptic patients with\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>\n                        1\n                        <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      <\/jats:italic>\n                      mutations. However, the mechanisms underlying these developmental disorders are poorly understood and treatments are currently unavailable. Using a rodent model with an\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\n                        cn1a\n                      <\/jats:italic>\n                      mutation, we aimed to elucidate the pathophysiologic basis and potential therapeutic treatments for developmental disorders stemming from\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\n                        cn1a\n                      <\/jats:italic>\n                      mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted behavioral analyses on rats with the\n                      <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\n                      1417\n                      <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>\n                      \u2010\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\n                        cn1a\n                      <\/jats:italic>\n                      mutation. With high\u2010performance liquid chromatography, we measured dopamine and its metabolites in the frontal cortex, striatum, nucleus accumbens, and midbrain. Methylphenidate was administered intraperitoneally to examine its effects on developmental disorder\u2013like behaviors and hyperthermia\u2010induced seizures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Behavioral studies revealed that\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\n                        cn1a\n                      <\/jats:italic>\n                      \u2010mutant rats had repetitive behavior, hyperactivity, anxiety\u2010like behavior, spatial learning impairments, and motor imbalance. Dopamine levels in the striatum and nucleus accumbens in\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\n                        cn1a\n                      <\/jats:italic>\n                      \u2010mutant rats were significantly lower than those in wild\u2010type rats. In\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\n                        cn1a\n                      <\/jats:italic>\n                      \u2010mutant rats, methylphenidate, by increasing dopamine levels in the synaptic cleft, improved hyperactivity, anxiety\u2010like behavior, and spatial learning impairments. Surprisingly, methylphenidate also strongly suppressed hyperthermia\u2010induced seizures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Dysfunction of the mesolimbic dopamine reward pathway may contribute to the hyperactivity and learning impairments in\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\n                        cn1a\n                      <\/jats:italic>\n                      \u2010mutant rats. Methylphenidate was effective for treating hyperactivity, learning impairments, and hyperthermia\u2010induced seizures. We propose that methylphenidate treatment may ameliorate not only developmental disorders but also epileptic seizures in patients with\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>\n                        1\n                        <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      <\/jats:italic>\n                      mutations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.12750","type":"journal-article","created":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T14:05:53Z","timestamp":1408975553000},"page":"1558-1567","source":"Crossref","is-referenced-by-count":15,"title":["Methylphenidate improves learning impairments and hyperthermia\u2010induced seizures caused by an\n                    <i>\n                      <scp>S<\/scp>\n                      cn1a\n                    <\/i>\n                    mutation"],"prefix":"10.1111","volume":"55","author":[{"given":"Iori","family":"Ohmori","sequence":"first","affiliation":[{"name":"Department of Physiology Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"},{"name":"Department of Medical Ethics Graduate School and Faculty of Medicine Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Physiology Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama 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