Abstract |
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 Y1 ([Leu31Pro34]NPY, 2.5 nmol), Y2 (Ac[Leu(28,31)]NPY24-36, 3 nmol), Y5 receptors [hPP1(-17),Ala31,Aib32]NPY, 4 nmol), NPY (3 nmol) or vehicle; and following (ii) i.c.v. injection of antagonists of Y1 ( BIBP3226, 20 nmol), Y2 ( BIIE0246, 20 nmol) and Y5 ( NPY5RA972, 20 nmol) receptors or vehicle, followed by NPY (3 nmol). Injection of the Y1- and Y5-selective agonists resulted in significantly less mean seizure suppression (37.4% and 53.9%, respectively) than NPY (83.2%; P < 0.05), while the Y2 agonist had similar effects to NPY (62.3% suppression, P = 0.57). Food intake was not increased following injection of the Y2 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 Y1 and Y5 antagonists (45.3% and 80.1%, respectively, P < 0.05), but not following the Y2 antagonist (5.1% suppression, P = 0.46). We conclude that NPY Y2 receptors are more important than Y1 and Y5 receptors in mediating the effect of NPY to suppress absence seizures in a genetic rat model. Y2 receptor agonists may represent targets for novel drugs against genetic generalized epilepsies without resulting in appetite stimulation.
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Authors | Margaret J Morris, Emma Gannan, Leanne M Stroud, Annette G Beck-Sickinger, Terence J O'Brien |
Journal | The European journal of neuroscience
(Eur J Neurosci)
Vol. 25
Issue 4
Pg. 1136-43
(Feb 2007)
ISSN: 0953-816X [Print] France |
PMID | 17331209
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Neuropeptide Y
- Receptors, Neuropeptide Y
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Topics |
- Analysis of Variance
- Animals
- Disease Models, Animal
- Drug Interactions
- Electroencephalography
(methods)
- Epilepsy, Absence
(drug therapy, genetics)
- Male
- Neuropeptide Y
(agonists, analogs & derivatives, therapeutic use)
- Rats
- Rats, Mutant Strains
- Receptors, Neuropeptide Y
(agonists, genetics, physiology)
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