title: Administration of the Y2 receptor agonist PYY3-36 in mice induces multiple behavioral changes relevant to schizophrenia.
abstract: Functional changes in neuropeptide Y (NPY) signaling at the Y2 receptor subtype have been widely implicated in stress-related neuropsychiatric illnesses such as depression and anxiety disorders. Altered Y2 receptor signaling may also play a role in the precipitation of behavioral and cognitive symptoms associated with schizophrenia. To seek preclinical evidence for this possibility, we explored the functional consequences of treatment with the selective Y2 receptor agonist PYY(3-36) using translational tests for the assessment of schizophrenia-relevant behavioral and cognitive deficits in mice. We found that acute systemic administration of PYY(3-36) at a low dose (1 μg/100 g body weight) or high dose (20 μg/100 g body weight) profoundly impaired social interaction without affecting innate anxiety. PYY(3-36) treatment at the high dose further led to a disruption of sensorimotor gating in the form of prepulse inhibition deficiency. This effect was fully antagonized by acute treatment with the preferential dopamine D2 receptor antagonist haloperidol, but not with clozapine. In addition, both doses of PYY(3-36) impaired selective associative learning in the latent inhibition paradigm and spatial working memory in a matching-to-position water maze test. The wide range of abnormalities induced by PYY(3-36) suggests that signaling at the Y2 subtype of NPY receptors is critical for a number of behavioral and cognitive functions, some of which are highly relevant to schizophrenia and related psychotic disorders. At least some of the behavioral deficits induced by augmentation of Y2 receptor signaling may involve increased dopaminergic activity.
authors.affiliation: Physiology and Behavior Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, Schwerzenbach, Switzerland.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Stadlbauer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
authors.forename: Urs
authors.initials: U
authors.lastname: Meyer
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007266:Inhibition, Psychological; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D019894:Peptide YY / Q000008:administration & dosage / Q000633:toxicity*; D017476:Receptors, Neuropeptide Y / Q000819:agonists*; D012559:Schizophrenia / Q000139:chemically induced*; D012919:Social Behavior
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D019894:Peptide YY; C061785:peptide YY (3-36); D003024:Clozapine; D006220:Haloperidol