Abnormal response to stress and impaired NPS-induced hyperlocomotion, anxiolytic effect and corticosterone increase in mice lacking NPSR1.
NPSR1 is a G protein coupled receptor expressed in multiple brain regions involved in modulation of stress. Central administration of NPS, the putative endogenous ligand of NPSR1, can induce hyperlocomotion, anxiolytic effects and activation of the HPA axis. The role of NPSR1 in the brain remains unsettled. Here we used NPSR1 gene-targeted mice to define the functional role of NPSR1 under basal conditions on locomotion, anxiety- and/or depression-like behavior, corticosterone levels, acoustic startle with prepulse inhibition, learning and memory, and under NPS-induced locomotor activation, anxiolysis, and corticosterone release. Male, but not female, NPSR1-deficient mice exhibited enhanced depression-like behavior in a forced swim test, reduced acoustic startle response, and minor changes in the Morris water maze. Neither male nor female NPSR1-deficient mice showed alterations of baseline locomotion, anxiety-like behavior, or corticosterone release after exposure to a forced swim test or methamphetamine challenge in an open-field. After intracerebroventricular (ICV) administration of NPS, NPSR1-deficient mice failed to show normal NPS-induced increases in locomotion, anxiolysis, or corticosterone release compared with WT NPS-treated mice. These findings demonstrate that NPSR1 is essential in mediating NPS effects on behavior.
Zhu
Hongyan
H
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Mingler
Melissa K
MK
McBride
Melissa L
ML
Murphy
Andrew J
AJ
Valenzuela
David M
DM
Yancopoulos
George D
GD
Williams
Michael T
MT
Vorhees
Charles V
CV
Rothenberg
Marc E
ME
D000223:Adaptation, Psychological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism; D001007:Anxiety / Q000097:blood / Q000235:genetics*; D003345:Corticosterone / Q000097:blood* / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006948:Hyperkinesis / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D013312:Stress, Physiological / Q000235:genetics* / Q000502:physiology; D013550:Swimming; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D014151:Anti-Anxiety Agents; C515062:NPSR1 protein, mouse; D009479:Neuropeptides; D043562:Receptors, G-Protein-Coupled; C539972:neuropeptide S, mouse; D003345:Corticosterone