Neuropeptide Y in the central nucleus of amygdala regulates the anxiolytic effect of agmatine in rats

Abstract In the present study, modulation of anxiolytic action of agmatine by neuropeptide Y (NPY) in the central nucleus of amygdala (CeA) is evaluated employing Vogel's conflict test (VCT) in rats. The intra-CeA administration of agmatine (0.6 and 1.2 µmol/rat), NPY (10 and 20 pmol/rat) or NPY Y1/Y5 receptors agonist [Leu31 , Pro34 ]-NPY (30 and 60 pmol/rat) significantly increased the number of punished drinking licks following 15 min of treatment. Combination treatment of subeffective dose of NPY (5 pmol/rat) or [Leu31 , Pro34 ]-NPY (15 pmol/rat) and agmatine (0.3 µmol/rat) produced synergistic anxiolytic-like effect. However, intra-CeA administration of selective NPY Y1 receptor antagonist, BIBP3226 (0.25 and 0.5 mmol/rat) produced anxiogenic effect. In separate set of experiment, pretreatment with BIBP3226 (0.12 mmol/rat) reversed the anxiolytic effect of agmatine (0.6 µmol/rat). Furthermore, we evaluated the effect of intraperitoneal injection of agmatine (40 mg/kg) on NPY-immunoreactivity in the nucleus accumbens shell (AcbSh), lateral part of bed nucleus of stria terminalis (BNSTl) and CeA. While agmatine treatment significantly decreased the fibers density in BNSTl, increase was noticed in AcbSh. In addition, agmatine reduced NPY-immunoreactive cells in the AcbSh and CeA. Immunohistochemical data suggest the enhanced transmission of NPY from the AcbSh and CeA. Taken together, this study suggests that agmatine produced anxiolytic effect which might be regulated via modulation of NPYergic system particularly in the CeA.