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However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking. We investigated the role of adult hippocampal neurogenesis in reducing cocaine voluntary intake produced by repeated cannabidiol treatment in mice. Cocaine intake was modelled using the intravenous cocaine self\u2010administration procedure in CD1 male mice. Cannabidiol (20\u00a0mg\/kg) reduced cocaine self\u2010administration behaviour acquisition and total cocaine intake and enhanced adult hippocampal neurogenesis. Our results show that a 6\u2010day repeated temozolomide treatment (25\u00a0mg\/kg\/day), a chemotherapy drug that blocks hippocampal neurogenesis, prevented cannabidiol\u2010induced increment in the early stages of neuronal maturation and differentiation, without altering the basal levels of BrdU\/NeuN and doublecortin immunostaining. The reduction of total cocaine intake and operant behaviour acquisition observed following cannabidiol exposure was attenuated by temozolomide treatment. Our results also show a similar effect of temozolamide on a cannabidiol\u2010induced improvement of novel object recognition memory, a task influenced by the proneurogenic effects of cannabidiol (10 and 20\u00a0mg\/kg). The anxiolytic effects of cannabidiol (10 and 20\u00a0mg\/kg), however, remained unaffected after its proneurogenic effects decreased. The present study confirms that adult hippocampal neurogenesis is one of the mechanisms by which cannabidiol lowers cocaine reinforcement and demonstrates the functional implication of adult hippocampal neurogenesis in cocaine voluntary consumption in mice. Such findings highlight the possible use of cannabidiol for developing new pharmacotherapies to manage cocaine use disorders.<\/jats:p>","DOI":"10.1111\/adb.12778","type":"journal-article","created":{"date-parts":[[2019,6,4]],"date-time":"2019-06-04T16:55:03Z","timestamp":1559667303000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake"],"prefix":"10.1111","volume":"25","author":[{"given":"Miguel \u00c1ngel","family":"Luj\u00e1n","sequence":"first","affiliation":[{"name":"Neurobiology of Behaviour Research Group (GReNeC\u2014NeuroBio), Department of Experimental and Health Sciences Universitat Pompeu Fabra  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00eddia","family":"Cantacorps","sequence":"additional","affiliation":[{"name":"Neurobiology of 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