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

Prog Neuropsychopharmacol Biol Psychiatry. 2023 Apr 20:123:110699. doi: 10.1016/j.pnpbp.2022.110699. Epub 2022 Dec 21.

Abstract

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.

Keywords: Adolescence; Affective behaviour; Alcohol; CGRP; NPY.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking*
  • Animals
  • Brain / metabolism
  • Calcitonin Gene-Related Peptide* / metabolism
  • Ethanol / metabolism
  • Male
  • Neuropeptide Y* / metabolism
  • Rats
  • Weight Gain

Substances

  • Calcitonin Gene-Related Peptide
  • Ethanol
  • Neuropeptide Y