In conclusion, the present study shows that complex plastic changes take place in NPY system during ACD binge treatment and subsequent withdrawal in the rat hippocampal formation and NAcc; we hypothesize that ACD binge treatment increases endocannabinoidergic transmission, similar to alcohol (94), thus resulting in a downregulation of NPY system that plays a role in physical dependence and in the onset of withdrawal syndrome. This evidence concerns the gene NPY and substance withdrawal syndrome.