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It has been shown that cannabidiol attenuates cue\u2010induced reinstatement of heroin seeking. However, to the best of our knowledge, its effects on brain stimulation reward and the reward\u2010facilitating effects of drugs of abuse have not yet been examined. Therefore, we investigated the effects of cannabidiol on brain reward function and on the reward\u2010facilitating effect of morphine and cocaine using the intracranial self\u2010stimulation (<jats:styled-content style=\"fixed-case\">ICSS<\/jats:styled-content>) paradigm. Rats were prepared with a stimulating electrode into the medial forebrain bundle (<jats:styled-content style=\"fixed-case\">MFB<\/jats:styled-content>), and a guide cannula into the dorsal raphe (microinjection experiments), and were trained to respond for electrical brain stimulation. A low dose of cannabidiol did not affect the reinforcing efficacy of brain stimulation, whereas higher doses significantly elevated the threshold frequency required for<jats:styled-content style=\"fixed-case\">MFB ICSS<\/jats:styled-content>. Both cocaine and morphine lowered<jats:styled-content style=\"fixed-case\">ICSS<\/jats:styled-content>thresholds. Cannabidiol inhibited the reward\u2010facilitating effect of morphine, but not cocaine. This effect was reversed by pre\u2010treatment with an intra\u2010dorsal raphe injection of the selective<jats:styled-content style=\"fixed-case\">5\u2010HT<jats:sub>1A<\/jats:sub><\/jats:styled-content>receptor antagonist<jats:styled-content style=\"fixed-case\">WAY<\/jats:styled-content>\u2010100635. The present findings indicate that cannabidiol does not exhibit reinforcing properties in the<jats:styled-content style=\"fixed-case\">ICSS<\/jats:styled-content>paradigm at any of the doses tested, while it decreases the reward\u2010facilitating effects of morphine. These effects were mediated by activation of<jats:styled-content style=\"fixed-case\">5\u2010HT<jats:sub>1A<\/jats:sub><\/jats:styled-content>receptors in the dorsal raphe. Our results suggest that cannabidiol interferes with brain reward mechanisms responsible for the expression of the acute reinforcing properties of opioids, thus indicating that cannabidiol may be clinically useful in attenuating the rewarding effects of opioids.<\/jats:p>","DOI":"10.1111\/j.1369-1600.2012.00483.x","type":"journal-article","created":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T17:39:06Z","timestamp":1344015546000},"page":"286-296","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":122,"title":["Cannabidiol inhibits the reward\u2010facilitating effect of morphine: involvement of<scp>5\u2010HT<sub>1A<\/sub><\/scp>receptors in the dorsal raphe nucleus"],"prefix":"10.1111","volume":"18","author":[{"given":"Vicky","family":"Katsidoni","sequence":"first","affiliation":[{"name":"Laboratory of Behavioral Neuroscience Department of Psychology School of Social Science University of Crete Rethymno Crete 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