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Its drug abuse potential was investigated using\n                      <jats:italic>in vivo<\/jats:italic>\n                      models in rodents and monkeys and compared with those of\n                      <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>\n                      odafinil, a psychostimulant currently used in the same indications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Effects of\n                      <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\n                      itolisant on dopamine release in the nucleus accumbens, on spontaneous and cocaine\u2010induced locomotion, locomotor sensitization were monitored. It was also tested in three standard drug abuse tests i.e. conditioned place preference in rats, self\u2010administration in monkeys and cocaine discrimination in mice as well as in a physical dependence model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Pitolisant did not elicit any significant changes in dopaminergic indices in rat nucleus accumbens whereas\n                      <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>\n                      odafinil increased dopamine release. In rodents,\n                      <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\n                      itolisant was without any effect on locomotion and reduced the cocaine\u2010induced hyperlocomotion. In addition, no locomotor sensitization and no conditioned hyperlocomotion were evidenced with this compound in rats whereas significant effects were elicited by\n                      <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>\n                      odafinil. Finally,\n                      <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\n                      itolisant was devoid of any significant effects in the three standard drug abuse tests (including self\u2010administration in monkeys) and in the physical dependence model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      No potential drug abuse liability for\n                      <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\n                      itolisant was evidenced in various\n                      <jats:italic>in vivo<\/jats:italic>\n                      rodent and primate models, whereas the same does not seem so clear in the case of\n                      <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>\n                      odafinil.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.12149","type":"journal-article","created":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T08:20:34Z","timestamp":1362730834000},"page":"632-644","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Preclinical evaluation of the abuse potential of\n                    <scp>P<\/scp>\n                    itolisant, a histamine\n                    <scp>H<\/scp>\n                    <sub>3<\/sub>\n                    receptor inverse agonist\/antagonist compared with\n                    <scp>M<\/scp>\n                    odafinil"],"prefix":"10.1111","volume":"169","author":[{"given":"M","family":"Uguen","sequence":"first","affiliation":[{"name":"Bioprojet\u2010Biotech Saint Gr\u00e9goire Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Perrin","sequence":"additional","affiliation":[{"name":"Bioprojet\u2010Biotech Saint Gr\u00e9goire Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Belliard","sequence":"additional","affiliation":[{"name":"Bioprojet\u2010Biotech Saint Gr\u00e9goire Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Ligneau","sequence":"additional","affiliation":[{"name":"Bioprojet\u2010Biotech Saint Gr\u00e9goire Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PM","family":"Beardsley","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Virginia Commonwealth University Richmond VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JM","family":"Lecomte","sequence":"additional","affiliation":[{"name":"Bioprojet\u2010Biotech Saint Gr\u00e9goire Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JC","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Bioprojet\u2010Biotech Saint Gr\u00e9goire Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-010-1839-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705964"},{"key":"e_1_2_7_4_1","first-page":"953","article-title":"The self\u2010administration of MK\u2010801 can depend upon drug\u2010reinforcement history, and its discriminative stimulus properties are phencyclidine\u2010like in rhesus monkeys","volume":"252","author":"Beardsley PM","year":"1990","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2009.05.028"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2004.11.029"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0603-0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)90498-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-002-1080-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2004.06.032"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.03.044"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300276"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.078303"},{"key":"e_1_2_7_14_1","unstructured":"European Medicines Agency EMA\/725532\/2010 rev(2011).Questions and answers on the review of medicines containing modafinil. 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