Plastic changes in neuropeptide Y receptor subtypes in experimental modelsof limbic seizures

Purpose: Neuropetide Y (NPY)-mediated neurotransmission in the hippocampus is altered by limbic seizures. The functional consequences of this change a re still unresolved and clearly depend on the type of NPY receptors involve d. NPY Y-2 and Y-1 receptors are increased on mossy fiber terminals and dec reased on granule cell dendrites after seizures, respectively. We investiga ted (a) whether seizures modify the NPY Y-5 receptors in the hippocampus, a nd (b) the effect of an agonist at Y-2/Y-5 receptors and antagonists at Y-1 receptors on acute and chronic seizure susceptibility. Methods: Limbic seizures were induced in rats by electrical stimulation of the dorsal hippocampus, leading to stage 5 kindled seizures, or by intrahip pocampal or systemic injections of kainic acid. Pentylentetrazol was admini stered to epileptic rats to assess their enhanced susceptibility to seizure s. NPY Y-5 receptor protein was measured in hippocampal homogenates using a specific polyclonal antibody and quantitative Western blotting. Results: Y5 receptors (57-kD band) were transiently decreased (23 to 35%) i n all hippocampal subregions 2 and 7 days, but not 2.5 hours, after seizure s induced by systemic kainic acid. A minor band of 51 kD was reduced signif icantly in CA3 and dentate gyrus, although it was increased in CA1, 30 days after seizures, suggesting long-term posttranslational changes in this pro tein. NPY Y-5 receptors were increased by 200% in total homogenate from the stimulated hippocampus 2 days but not 30 days after fully kindled seizures . Intracerebral injections of NPY 13-36 (Y-2/Y-5 receptor agonist) or BIBP 3225 and BIBO 3304 (selective Y-1 receptor antagonists) decreased seizure s usceptibility in rats. Conclusions: These results indicate that NPY Y-5 receptors change after lim bic seizures and suggest that NPY receptors may provide novel target(s) for the treatment of epilepsy.