2003) and it is consistent with the anxiogenic-like effects of intra-amygdala treatment of Y2-preferring agonists in the rat social interaction test (Sajdyk et al., 1999). A novel brain-penetrant Y2-antagonist has been examined, however the results were negative (unpublished data) while the study reproduced previously published results (Rimondini et al., 2005). Also, intra-amygdala administration of a viral vector designed to over-express NPY was found to have anxiolytic-like properties and suppressed ethanol intake in the treated animals (Thorsell et al., 2007). As seen for the anxiolytic-like effects of NPY, the effects appear to be activity dependent. In summary, increasing NPY-levels or administering an antagonist to the presynaptic Y2-receptor, and thereby theoretically increasing the availability of NPY in the synaptic cleft, does decrease ethanol intake primarily in animals with a history of alcohol exposure. Thus, targeting the NPY system, possibly through antagonism at pre-synaptic Y2 auto-receptors, may still offer an attractive strategy for developing novel antidepressant and anti-anxiety treatments.
