title: Anxiolytic-like effects after vector-mediated overexpression of neuropeptide Y in the amygdala and hippocampus of mice.
abstract: Neuropeptide Y (NPY) causes anxiolytic- and antidepressant-like effects after central administration in rodents. These effects could theoretically be utilized in future gene therapy for anxiety and depression using viral vectors for induction of overexpression of NPY in specific brain regions. Using a recombinant adeno-associated viral (rAAV) vector, we addressed this idea by testing effects on anxiolytic- and depression-like behaviours in adult mice after overexpression of NPY transgene in the amygdala and/or hippocampus, two brain regions implicated in emotional behaviours. In the amygdala, injections of rAAV-NPY caused significant anxiolytic-like effect in the open field, elevated plus maze, and light-dark transition tests. In the hippocampus, rAAV-NPY treatment was associated with anxiolytic-like effect only in the elevated plus maze. No additive effect was observed after combined rAAV-NPY injection into both the amygdala and hippocampus where anxiolytic-like effect was found in the elevated plus maze and light-dark transition tests. Antidepressant-like effects were not detected in any of the rAAV-NPY injected groups. Immobility was even increased in the tail suspension and forced swim tests after intra-amygdaloid rAAV-NPY. Taken together, the present data show that rAAV-NPY treatment may confer non-additive anxiolytic-like effect after injection into the amygdala or hippocampus, being most pronounced in the amygdala.
authors.affiliation: Laboratory for Neural Plasticity, Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
authors.forename: S H
authors.initials: SH
authors.lastname: Christiansen
authors.affiliation: Laboratory for Neural Plasticity, Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
authors.forename: M V
authors.initials: MV
authors.lastname: Olesen
authors.affiliation: Laboratory for Neural Plasticity, Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
authors.forename: C R
authors.initials: CR
authors.lastname: Gøtzsche
authors.affiliation: Laboratory for Neural Plasticity, Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark. Electronic address: woldbye@sund.ku.dk.
authors.forename: D P D
authors.initials: DP
authors.lastname: Woldbye
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001007:Anxiety / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D000229:Dependovirus / Q000235:genetics*; D003863:Depression / Q000235:genetics / Q000378:metabolism / Q000821:virology; D005822:Genetic Vectors / Q000008:administration & dosage*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D009043:Motor Activity; D009478:Neuropeptide Y / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014151:Anti-Anxiety Agents; D009478:Neuropeptide Y
keywords: Amygdala; Anxiety; Depression; Hippocampus; rAAV-NPY