Abstrakt: |
Alcohol binge drinking is common among adolescents and may challenge the signalling systems that process affective stimuli, including calcitonin gene‐related peptide (CGRP) signalling. Here, we employed a rat model of adolescent binge drinking to evaluate reward‐, social‐ and aversion‐related behaviour, glucocorticoid output and CGRP levels in affect‐related brain regions. As a potential rescue, the effect of the phytocannabinoid cannabidiol was explored. Adolescent male rats underwent the intermittent 20% alcohol two‐bottle choice paradigm; at the binge day (BD) and the 24 h withdrawal day (WD), we assessed CGRP expression in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala, hypothalamus and brainstem; in addition, we evaluated sucrose preference, social motivation and drive, nociceptive response, and serum corticosterone levels. Cannabidiol (40 mg/kg, i.p.) was administered before each drinking session, and its effect was measured on the above‐mentioned 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‐ 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‐related hyper‐responsivity, as well as glucocorticoid levels in alcohol binge‐like drinking rats. Overall, CGRP can represent both a mediator and a target of alcohol binge‐like drinking and provides a further piece in the intricate puzzle of alcohol‐induced behavioural and neuroendocrine sequelae. CBD shows promising effects in limiting adolescent alcohol binge drinking and rebalancing the bio‐behavioural abnormalities. [ABSTRACT FROM AUTHOR] |