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Neuropeptide Y suppresses absence seizures in a genetic rat model primarily through effects on Y 2 receptors
Author(s) -
Morris Margaret J.,
Gannan Emma,
Stroud Leanne M.,
BeckSickinger Annette G.,
O'Brien Terence J.
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05348.x
Subject(s) - neuropeptide y receptor , medicine , endocrinology , agonist , receptor , epilepsy , antagonist , chemistry , genetic model , receptor antagonist , neuropeptide , biology , neuroscience , biochemistry , gene
Neuropeptide Y (NPY) potently suppresses absence seizures in a model of genetic generalized epilepsy, genetic absence epilepsy rats of Strasbourg (GAERS). Here we investigated the Y‐receptor subtype(s) on which NPY exerts this anti‐absence effect. A dual in vivo approach was used: the cumulative duration of seizures was quantified in adult male GAERS in 90‐min electroencephalogram recordings following intracerebroventricular (i.c.v.) injection of: (i) subtype‐selective agonists of Y 1 ([Leu 31 Pro 34 ]NPY, 2.5 nmol), Y 2 (Ac[Leu 28,31 ]NPY24–36, 3 nmol), Y 5 receptors [hPP1 −17 ,Ala 31 ,Aib 32 ]NPY, 4 nmol), NPY (3 nmol) or vehicle; and following (ii) i.c.v. injection of antagonists of Y 1 (BIBP3226, 20 nmol), Y 2 (BIIE0246, 20 nmol) and Y 5 (NPY5RA972, 20 nmol) receptors or vehicle, followed by NPY (3 nmol). Injection of the Y 1 ‐ and Y 5 ‐selective agonists resulted in significantly less mean seizure suppression (37.4% and 53.9%, respectively) than NPY (83.2%; P < 0.05), while the Y 2 agonist had similar effects to NPY (62.3% suppression, P = 0.57). Food intake was not increased following injection of the Y 2 agonist, while significant increases in food intake were seen following NPY and the other Y‐subtype agonists. Compared with vehicle, NPY injection suppressed seizures following the Y 1 and Y 5 antagonists (45.3% and 80.1%, respectively, P < 0.05), but not following the Y 2 antagonist (5.1% suppression, P = 0.46). We conclude that NPY Y 2 receptors are more important than Y 1 and Y 5 receptors in mediating the effect of NPY to suppress absence seizures in a genetic rat model. Y 2 receptor agonists may represent targets for novel drugs against genetic generalized epilepsies without resulting in appetite stimulation.