Behavioral effects of neuropeptide Y receptor agonists in the elevated plus-maze and fear-potentiated startle procedures

Abstract

Evidence from animal studies has led to the proposal that neuropeptide Y (NPY) has anxiolytic-like effects in rats after intracerebroventricular (i.c.v.) administration. The purpose of the present study was to extend these observations by examining the behavioral effects of a series of NPY receptor agonists including NPY, peptidc YY (PYY), the NPY fragment 2–36 (NPY_2–36), the Y₁ agonist [Leu³¹, Pro³⁴]-NPY and the Y₂ agonist NPY fragment 13–36 (NPY_13–36), in two established anxiety models in rats: the elevated plus-naze and the fear-potentiated startle procedures. In the elevated plus-maze procedure, i.t.v. PYY (0.07–2.3 nmol), NPY (0.07–2.3 nmol), NPY_2–36 (0.07–2.3 nmol). [Leu³¹, Pro³⁴]-NPY (0.7–7 nmol), but not NPY_13–36 (0.7–7 nmol), increased preference for the open arms of the plus-maze in a dose-dependent manner. In an acoustic startle paradigm, NPY, PYY and NPY_2–36 inhibited fear-potentiated startle over the dose-range of 0.23–2.3 nmol. [Leu³¹, Pro³⁴]-NPY (2.3–13.2 nmol) also attenuated fear-potentiated startle, whereas NPY_13–36 (up to 13.2 nmol) had no effect. Taken together, these findings demonstrate that NPY, PYY and NPY_2–36 have anxiolytic-like effects that are likely mediated by Y₁ receptors.