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To address this issue, we exposed laboratory rats to subchronic regimens of heroin or cocaine and tested long\u2010term effects on (i) depressive\u2010like behaviors, (ii) brain\u2010derived neurotrophic factor (<jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content>) levels in reward\u2010related brain regions, and (iii) depressive\u2010like behavior following an additional chronic mild stress procedure. The long\u2010term effect of subchronic cocaine exposure was a general reduction in locomotor activity whereas heroin exposure induced a more specific increase in immobility during the forced swim test. Both cocaine and heroin exposure induced alterations in <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content> levels that are similar to those observed in several animal models of depression. Finally, both cocaine and heroin exposure significantly enhanced the anhedonic effect of chronic mild stress. These results suggest that subchronic drug exposure induces depressive\u2010like behavior which is accompanied by modifications in <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content> expression and increases the vulnerability to develop depressive\u2010like behavior following chronic stress. Implications for recreational and small\u2010scale drug users are discussed.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12753-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><jats:p>In the present study, we examined the long\u2010term effects of limited subchronic drug exposure on depressive\u2010like symptoms. Our results demonstrate that short\u2010term, subchronic administration of either cocaine or heroin promotes some depressive\u2010like behaviors, while inducing alterations in BDNF protein levels similar to alterations observed in several animal models of depression. In addition, subchronic cocaine or heroin enhanced the anhedonic effect of chronic stress.<\/jats:p>","DOI":"10.1111\/jnc.12753","type":"journal-article","created":{"date-parts":[[2014,5,5]],"date-time":"2014-05-05T11:39:11Z","timestamp":1399289951000},"page":"575-582","source":"Crossref","is-referenced-by-count":20,"title":["Induction of depressive\u2010like effects by subchronic exposure to cocaine or heroin in laboratory rats"],"prefix":"10.1111","volume":"130","author":[{"given":"Noga","family":"Zilkha","sequence":"first","affiliation":[{"name":"Department of Neurobiology Weizmann institute of Science Rehovot Israel"},{"name":"Department of Life Sciences Ben\u2010Gurion University Beer\u2010Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Feigin","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Ben\u2010Gurion University Beer\u2010Sheva 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