ANXIOLYTIC-LIKE ACTION OF NEUROPEPTIDE-Y - MEDIATION BY Y1 RECEPTORS IN AMYGDALA, AND DISSOCIATION FROM FOOD-INTAKE EFFECTS

Evidence from animal and human studies suggests that neuropeptide Y (N PY) may be a potent endogenous anxiolytic. The anatomic structures med iating this action of the peptide remain unknown. Furthermore, in addi tion to its anxiolytic-like effects, intracerebroventricular administr ation of NPY induces food intake through hypothalamic mechanisms, maki ng the anxiolytic-like action of the peptide more difficult to interpr et. The purpose of this study was to examine the anatomic substrate fo r the effects of NPY on anxiety, and to characterize the NPY receptors mediating these effects. Intracerebroventricular injection of NPY pro duced increased food intake in free-feeding animals, and dose-dependen t anticonflict/anxiolytic-like effects in an established animal model of anxiety, the Geller-Seifter punished responding test. In contrast, microinjection of NPY into the central nucleus of the amygdala did not increase food intake in free-feeding animals, did not affect unpunish ed lever pressing for food, but did reproduce the anticonflict/anxioly tic-like effect with high potency. The selective NPY-Y1 agonist, p[Leu 31,Pro34]NPY was approximately equipotent with native NPY in the confl ict paradigm, and markedly more potent than the Y2 agonist, NPY13-36. Intrastriatal injections had no effect on conflict behavior. Thus, act ivation of Y1 receptors in the central nucleus of the amygdala produce s effects similar to established anxiolytics without affecting food in take, suggesting that Y1-receptors in the amygdala may be a substrate for anxiolytic actions of NPY.