title: Y5 neuropeptide Y receptor overexpression in mice neither affects anxiety- and depression-like behaviours nor seizures but confers moderate hyperactivity.
abstract: Neuropeptide Y (NPY) has been implicated in anxiolytic- and antidepressant-like behaviour as well as seizure-suppressant effects in rodents. Although these effects appear to be predominantly mediated via other NPY receptors (Y1 and/or Y2), several studies have also indicated a role for Y5 receptors. Gene therapy using recombinant viral vectors to induce overexpression of NPY, Y1 or Y2 receptors in the hippocampus or amygdala has previously been shown to modulate emotional behaviour and seizures in rodents. The present study explored the potential effects of gene therapy with the Y5 receptor, by testing effects of recombinant adeno-associated viral vector (rAAV) encoding Y5 (rAAV-Y5) in anxiety- and depression-like behaviour as well as in kainate-induced seizures in adult mice. The rAAV-Y5 vector injected into the hippocampus and amygdala induced a pronounced and sustained increase in Y5 receptor mRNA expression and functional Y5 receptor binding, but no significant effects were found with regard to anxiety- and depression-like behaviours or seizure susceptibility. Instead, rAAV-mediated Y5 receptor transgene overexpression resulted in moderate hyperactivity in the open field test. These results do not support a potential role for single transgene overexpression of Y5 receptors for modulating anxiety-/depression-like behaviours or seizures in adult mice. Whether the induction of hyperactivity by rAAV-Y5 could be relevant for other conditions remains to be studied.
authors.affiliation: Protein Laboratory & Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M V
authors.initials: MV
authors.lastname: Olesen
authors.forename: S H
authors.initials: SH
authors.lastname: Christiansen
authors.forename: C R
authors.initials: CR
authors.lastname: Gøtzsche
authors.forename: B
authors.initials: B
authors.lastname: Holst
authors.forename: M
authors.initials: M
authors.lastname: Kokaia
authors.forename: D P D
authors.initials: DP
authors.lastname: Woldbye
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D003863:Depression / Q000503:physiopathology*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006948:Hyperkinesis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor