Adolescent binge-like alcohol exposure dysregulates NPY and CGRP in rats: Behavioural and immunochemical evidence

Alcohol binge drinking during adolescence impacts affective behaviour, possibly impinging on developing neural substrates processing affective states, including calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY). Here, we modelled binge-like alcohol exposure in adolescence, by administering 3.5 g/kg alcohol per os, within 1 h, to male adolescent rats every other day, from postnatal day 35 to 54. The effects on positive and negative affective behaviour during abstinence were explored including: consummatory behaviour and weight gain; social behaviour in the modified social interaction test; thermal nociception in the tail-flick test; psychosocial stress coping in the resident-intruder paradigm. Moreover, CGRP and NPY levels were evaluated in functionally relevant brain regions. Our data shows that binge-like intermittent alcohol administration during adolescence decreased weight gain, social preference and motivation, nociception, and active psychosocial stress coping during abstinence. In addition, intermittent alcohol-exposed rats displayed increased expression of CGRP and NPY in the prefrontal cortex and nucleus accumbens; decreased NPY levels in the amygdala; opposite changes in CGRP levels in the hypothalamus and brainstem. Overall, our data shows that adolescent binge-like alcohol exposure, through the allostatic load of alternate intoxication and withdrawal, produces long-term consequences in sensory and affective processes and dysregulated complementary neuropeptidergic systems. Thus, neuropeptide-targeted interventions hold promising potential for addressing negative affect during prolonged withdrawal in young subjects.

Automated summary

Alcohol binge drinking during adolescence has negative impacts on affective behaviour and the development of neural substrates processing affective states. This study simulated adolescent binge-like alcohol exposure in male rats and examined its effects on various affective behaviours and neuropeptide levels in functionally relevant brain regions. The results showed that binge-like alcohol exposure during adolescence led to decreased weight gain, social preference, and active stress coping, as well as dysregulated neuropeptide levels in different brain regions. These findings suggest that neuropeptide-targeted interventions may be promising for addressing negative affect during prolonged withdrawal in young individuals.