title: Role of neuropeptide Y Y₁ and Y₂ receptors on behavioral despair in a rat model of depression with co-morbid anxiety.
abstract: Accumulated evidence suggests that neuropeptide Y (NPY) is involved in emotional disorders by acting on Y(1) and Y(2) receptors. This hypothesis is based on animal studies carried out in naïve normal animals but not in animal models of depression, including the olfactory bulbectomized (OBX) rat. The OBX rat produces a wide array of symptoms that mimic several aspects of human depression and anxiety disorders. In the present study, we aimed to investigate the effects of sustained (2 weeks) intracerebroventricular administration of NPY Y(1) and Y(2) agonists and antagonists in a battery of behavioral tests including the open field, forced swim test (FST) and social interaction (SI) tests in OBX rats. The levels of Y(1) and Y(2) receptors in the hippocampus and basolateral amygdala (BLA) were also evaluated. Treatment with the Y(1)-like receptor agonist, [Leu(31)Pro(34)]PYY, decreased both depressive- and anxiogenic-like behaviors. The Y(2) receptor antagonist, BIIE0246, decreased the immobility time in the FST in OBX animals and increased active contacts in the SI test in sham rats. The Y(2) agonist, PYY3-36, increased the immobility time in the FST in OBX rats. Additionally, increased levels of Y(2) receptor binding were quantified in the dorsal hippocampus and BLA in OBX rats. Taken together, the autoradiographic results add further evidence that the NPYergic system is altered in disturbed emotional states. Moreover, we demonstrate a differential role for NPY Y(1) and Y(2) receptors in emotional processes under control and challenged conditions. This article is part of a Special Issue entitled 'Anxiety and Depression'.
authors.affiliation: Department of Neurology & Neurosurgery, McGill University, Montréal, QC H4H 1R3, Canada.
authors.forename: Julio César
authors.initials: JC
authors.lastname: Morales-Medina
authors.forename: Yvan
authors.initials: Y
authors.lastname: Dumont
authors.forename: Charles-Etienne
authors.initials: CE
authors.lastname: Benoit
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bastianetto
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Flores
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: Rémi
authors.initials: R
authors.lastname: Quirion
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001345:Autoradiography; D001552:Benzazepines; D003863:Depression / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007398:Interpersonal Relations; D008297:Male; D009478:Neuropeptide Y / Q000031:analogs & derivatives; D009830:Olfactory Bulb / Q000502:physiology / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: D001552:Benzazepines; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C062259:neuropeptide Y, Leu(31)-Pro(34)-; D001120:Arginine; C403256:BIIE 0246; C117416:BIBO 3304