Behavioral and neurobiological changes within a period of heightened susceptibility to voluntary alcohol withdrawal

Abstract

In this study, we identify a time frame of increased susceptibility to voluntary alcohol withdrawal in rats, and we study the behavioral and neurobiological changes resulting from this withdrawal. Male Sprague Dawley rats were fed a liquid ethanol‐containing diet and their daily consumption was recorded. We determined that rats are most susceptible to fatal episodes of withdrawal within 10–20 days on the ethanol diet. Rats whose intake decreased severely within this period were determined to be experiencing voluntary alcohol withdrawal, and their behavior was videotaped and subsequently scored. Compared to involuntarily withdrawn chronic ethanol‐fed animals, the animals experiencing voluntary alcohol withdrawal also showed an array of behavioral signs and apparent homeostatic dysregulation to the point of death. In order to study the neurobiological changes associated with such perturbations in homeostatic and emotional control, we tested for and discovered differential gene expression in two brain regions: the nucleus tractus solitarius (NTS) and the central nucleus of the amygdala (CeA). We conclude that increased anxiety and the associated neurobiological changes may lead to the dangerous state of voluntary withdrawal, and future work will include the administration of anxiolytics to test this hypothesis. Research Support: NIH/NIAAA R01 AA13204 to JSS.