Neuropeptide Y (NPY) is a neuropeptide with dramatic anxiolytic-like properties localized to the amygdala and has been hypothesized to have opposite effects to CRF in the negative motivational state of withdrawal from drugs of abuse (Heilig and Koob, 2007). Significant evidence suggests that activation of NPY in the central nucleus of the amygdala can block the motivational aspects of dependence associated with chronic ethanol administration. NPY administered intracerebroventricularly blocked the increased drug intake associated with ethanol dependence (Thorsell et al., 2005a, b). Injection of NPY directly into the central nucleus of the amygdala (Gilpin et al., 2008) and viral vector-enhanced expression of NPY in the central nucleus of the amygdala also blocked the increased drug intake associated with ethanol dependence (Thorsell et al., 2007).
