title: Viral vector-mediated gene transfer of the vole V1a vasopressin receptor in the rat septum: improved social discrimination and active social behaviour.
abstract: This study explores the effects of enhancing vasopressin V1a receptor expression in the septum using viral vector-mediated gene transfer on social discrimination and social interactions. Bilateral infusion of an adeno-associated viral vector containing the prairie vole V1a receptor gene (V1aR-AAV) regulated by a neuron-specific enolase promoter resulted in a stable increase in V1a receptor binding density in the rat septum without affecting oxytocin receptor density. Control animals were infused with a vector expressing the lacZ gene. In a social discrimination paradigm, only V1aR-AAV-treated animals succeeded in discriminating a previously encountered from a novel juvenile after an interexposure interval (IEI) of more than 2 h, demonstrating the functional incorporation of the vole V1a receptor in the rat septal circuits underlying short-term memory processes. Microdialysis administration of synthetic vasopressin during the first juvenile exposure, used to mimic intraseptal release patterns of the neuropeptide, produced similar prolongations in recognition (up to an IEI of 24 h) in both V1aR-AAV and control animals. Septal microdialysis administration of a selective V1a, but not oxytocin, receptor antagonist in both groups prevented discrimination even after an IEI of as short as 0.5 h, confirming the specificity of the vole V1a receptor involvement in social discrimination abilities. In addition, active social interactions were found to be increased among V1aR-AAV rats compared to controls. Viral vector-mediated gene transfer provides a valuable tool for studies on the role of localized gene expression on behavioural parameters.
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstrasse 2, 80804 Munich, Germany. landgraf@mpipsykl.mpg.de
authors.forename: Rainer
authors.initials: R
authors.lastname: Landgraf
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Frank
authors.forename: John M
authors.initials: JM
authors.lastname: Aldag
authors.forename: Inga D
authors.initials: ID
authors.lastname: Neumann
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Sharer
authors.forename: Xianghui
authors.initials: X
authors.lastname: Ren
authors.forename: Ernest F
authors.initials: EF
authors.lastname: Terwilliger
authors.forename: Masanobu
authors.initials: M
authors.lastname: Niwa
authors.forename: Alexandra
authors.initials: A
authors.lastname: Wigger
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Young
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D003411:Arvicolinae; D001345:Autoradiography; D000229:Dependovirus / Q000235:genetics; D004192:Discrimination, Psychological / Q000187:drug effects; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007763:Lac Operon; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000235:genetics*; D020665:Septum of Brain / Q000502:physiology*; D012919:Social Behavior; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D014667:Vasopressins / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D014667:Vasopressins