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Here, we employed a rat model of adolescent binge drinking to evaluate reward\u2010, social\u2010 and aversion\u2010related behaviour, glucocorticoid output and CGRP levels in affect\u2010related brain regions. As a potential rescue, the effect of the phytocannabinoid cannabidiol was explored. Adolescent male rats underwent the intermittent 20% alcohol two\u2010bottle choice paradigm; at the binge day (BD) and the 24\u2009h withdrawal day (WD), we assessed CGRP expression in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala, hypothalamus and brainstem; in addition, we evaluated\u00a0sucrose preference, social motivation and drive, nociceptive response, and serum corticosterone levels. Cannabidiol (40\u2009mg\/kg, i.p.) was administered before each drinking session, and its effect was measured on the above\u2010mentioned readouts. At BD and WD, rats displayed decreased CGRP expression in mPFC, NAc and amygdala; increased CGRP levels in the brainstem; increased response to rewarding\u2010 and nociceptive stimuli and decreased social drive; reduced serum corticosterone levels. Cannabidiol reduced alcohol consumption and preference; normalised the abnormal corticolimbic CGRP expression, and the reward and aversion\u2010related hyper\u2010responsivity, as well as glucocorticoid levels in alcohol binge\u2010like drinking rats. Overall, CGRP can represent both a mediator and a target of alcohol binge\u2010like drinking and provides a further piece in the intricate puzzle of alcohol\u2010induced behavioural and neuroendocrine sequelae. CBD shows promising effects in limiting adolescent alcohol binge drinking and rebalancing the bio\u2010behavioural abnormalities.<\/jats:p>","DOI":"10.1002\/ptr.7972","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T06:24:43Z","timestamp":1690871083000},"page":"4870-4884","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cannabidiol tempers alcohol intake and neuroendocrine and behavioural correlates in alcohol binge drinking \u00a0adolescent rats. Focus on calcitonin gene\u2010related peptide's brain levels"],"prefix":"10.1002","volume":"37","author":[{"given":"Giuseppe","family":"Tringali","sequence":"first","affiliation":[{"name":"Pharmacology Section, Department of Health Care Surveillance and Bioethics Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Fondazione Policlinico Universitario A. 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D'Alessandro\u201d University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kuchar","sequence":"additional","affiliation":[{"name":"Forensic Laboratory of Biologically Active Compounds, Department of Chemistry of Natural Compounds University of Chemistry and Technology  Prague Czechia"},{"name":"Psychedelics Research Centre National Institute of Mental Health  Prague Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6726-6872","authenticated-orcid":false,"given":"Diego","family":"Curr\u00f2","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Health Care Surveillance and Bioethics Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Fondazione Policlinico Universitario A. 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