Brain NPY Y1 receptors rapidly mediate the behavioral response to novelty and a compartment-specific modulation of granulocyte function in blood and spleen

Abstract

Neuropeptide Y (NPY) alters behavioral activity and innate immune functions of rats within minutes of intracerebroventricular (i.c.v.) application. Using combinations of the Y1-5a,b(6) agonist NPY, the Y1,3,5 agonist [Leu31-Pro34]NPY (LP-NPY), and the selective Y1 antagonist BIBP3226 (BIBP), we investigated whether the NPY-Y1 receptor (Y1R) subtype regulates NPY-induced behavioral and immunological effects at 15 min after i.c.v. application. Administration of both NPY and LP-NPY decreased rearing activity in the open field and suppressed granulocyte function in the blood. These effects were blocked by BIBP pre-treatment. In contrast to the blood, NPY and BIBP+NPY treatments stimulated granulocyte function within the splenic compartment. In addition, a blood leukophilia composed of granulocytes and NK cells was induced by NPY only. We conclude that the tested early effects of NPY are mediated by either the Y1R (rearing, blood granulocyte function), or a non-Y1R (splenic granulocyte function), or by a combined receptor activation (leukocyte mobilization). Furthermore, the immunological effects of NPY demonstrate compartment specificity.