Evaluation of neuropeptide Y expression during acetaldehyde withdrawal in rats. Focus on hippocampus and nucleus accumbens

Abstract

Stress-related neuropeptides are involved in setting up alcohol addiction. Ethanol is able to acutely induce CRH and ACTH release, while cronically a dampered response of the hypothalamus -pituitary- adrenal (HPA) axis has been observed. Also neuropeptide Y (NPY) has been shown to modulate ethanol consumption, and its central expression seems inversely correlated to ethanol intake. Recent in vivo and in vitro evidence have highlighted the key role of acetaldehyde (ACD), ethanol first metabolite, as a mediator of the central effects of ethanol, even as modulator of the neuropeptidergic transmission in the rat brain. The aim of this study was to investigate NPY immunoreactivity following a 4-day binge ACD treatment in hippocampus and nucleus accumbens, two areas particulary involved in addictive-related learning and reward processes. Wistar rats have been intragastrically administered with ACD (450mg/kg) five times per day, for four days, and have been sacrificed at early (16h) and late (72h) withdrawal. Our results show: i) an increased NPY expression at 16h and 72h after the last administration in hippocampus (p< 0.001; p< 0.001) and nucleus accumbens (p< 0.05; p< 0.001) compared to controls. ii) an increase in the number of NPY-positive neurons in the hippocampus (p< 0.001) and nucleus accumbens (p< 0.001) in late withdrawal with respect to early withdrawal. These findings are consistent with the hypothesis that NPY levels increase in a time- and region-specific fashion to reset homeostasis in the brain during withdrawal; and that ACD is able to affect neuropeptidergic transmission as well as ethanol, playing thus a key role in the neuroadaptative changes that characterize ethanol addiction.