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It has been observed that chronic exposure to drugs of abuse produces molecular and cellular adaptations in ventral tegmental area (<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content>) neurons, mediated by brain\u2010derived neurotrophic factor (<jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content>). These <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content>\u2010induced adaptations in the <jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content> are associated with the establishment of aversive withdrawal motivation that leads to a drug\u2010dependent state. Growing evidence suggests that 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>2A<\/jats:sub> receptor signaling can regulate the expression of <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content> in the brain. In this study, we observed that a single systemic or intra\u2010<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content> administration of a 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>2A<\/jats:sub> agonist in rats and mice blocks both the aversive conditioned response to drug withdrawal and the mechanism responsible for switching from a drug\u2010naive to a drug\u2010dependent motivational system. Our results suggest that 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>2A<\/jats:sub> agonists could be used as therapeutic agents to reverse a drug dependent state, as well as inhibiting the aversive effects produced by drug withdrawal.<\/jats:p>","DOI":"10.1111\/ejn.13572","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T17:46:05Z","timestamp":1491414365000},"page":"1410-1417","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A single administration of the hallucinogen, 4\u2010acetoxy\u2010dimethyltryptamine, prevents the shift to a drug\u2010dependent state and the expression of withdrawal aversions in rodents"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9907-7192","authenticated-orcid":false,"given":"Hector","family":"Vargas\u2010Perez","sequence":"first","affiliation":[{"name":"Institute of Medical Science University of Toronto 1130\u2010160 College St Toronto ON M5S 3E1 Canada"},{"name":"The Nierika Intercultural Medicine Institute Ocuilan Estado de M\u00e9xico M\u00e9xico"},{"name":"Postgrado en Ciencias Cognitivas Universidad Autonoma del Estado de Morelos Cuernavaca Morelos M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4282-6049","authenticated-orcid":false,"given":"Taryn E.","family":"Grieder","sequence":"additional","affiliation":[{"name":"Institute of Medical Science University of Toronto 1130\u2010160 College St Toronto ON M5S 3E1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Ting\u2010A\u2010Kee","sequence":"additional","affiliation":[{"name":"Institute of Medical Science University of Toronto 1130\u2010160 College St Toronto ON M5S 3E1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geith","family":"Maal\u2010Bared","sequence":"additional","affiliation":[{"name":"Institute of Medical Science University of Toronto 1130\u2010160 College St Toronto ON M5S 3E1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Chwalek","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"van der Kooy","sequence":"additional","affiliation":[{"name":"Institute of Medical Science University of Toronto 1130\u2010160 College St Toronto ON M5S 3E1 Canada"},{"name":"Department of Molecular Genetics University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02763.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1037\/0735-7044.109.1.91","article-title":"Neurobiology of withdrawal motivation: evidence for two separate aversive effects produced in morphine\u2010naive versus morphine\u2010dependent rats by both naloxone and spontaneous withdrawal","volume":"109","author":"Bechara A.","year":"1995","journal-title":"Behav. 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