Several proteins and pathways have been described that modify the development of acute functional tolerance in different species. GABAA receptors isolated from ethanol-treated mice demonstrate acute tolerance in vitro [5], and this requires functional Protein Kinase Cε. In addition, Protein Kinase Cε knock out mice show defects in AFT [6]. In C. elegans, we have previously shown that the Neuropeptide Y Receptor-like protein, NPR-1, acts to negatively regulate the development of acute functional tolerance. This observation extends to the mouse, where animals with loss of function of various components of the brain NPY pathway recover more rapidly from hypnotic doses of ethanol [7], [8], a measure of the development of AFT in mice [9].
