Schizophrenia-relevant behaviours in a genetic mouse model for Y2 deficiency.
Expression levels of neuropeptide Y (NPY) are changed in schizophrenia patients. However, the direction of changes to NPY expression and the mechanisms behind NPY's impact on the development of the illness is not understood in detail. Here we investigated whether alterations in Y2 activity may be involved in the development of schizophrenia-related behaviours. We examined NPY Y2 receptor deficient male mice in behavioural domains relevant for the illness: locomotion, learning and memory, social interaction and sensorimotor gating (baseline and after acute challenge with psychotropic drugs) and the most relevant tasks were also completed in female Y2 mutants. Our investigations confirmed a hyper-locomotive phenotype for Y2 deficient male mice and no alterations in working and reference memory performance. Mutant males exhibited an increase in social interaction and moderately improved sensorimotor gating. The psychotropic drugs dexamphetamine and MK-801 affected prepulse inhibition similarly, whereas MK-801 appeared to be a slightly more potent stimulant for the acoustic startle response (ASR). Female Y2 deficient mice showed wild type-like performances in social interaction, working memory and prepulse inhibition. However, Y2 mutant females exhibited a moderately increased ASR compared to control mice. Taken together, lack of Y2 signalling in mice not only leads to altered locomotion but also changes social behaviours and affects sensorimotor gating. Thus, Y2 depletion influences a range of behaviours, which are potentially relevant for schizophrenia-related research.
Karl
Tim
T
Neuroscience Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia. t.karl@powmri.edu.au
Chesworth
Rose
R
Duffy
Liesl
L
Herzog
Herbert
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003913:Dextroamphetamine / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D007175:Impulsive Behavior / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009483:Neuropsychological Tests; D011619:Psychotropic Drugs / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D012565:Schizophrenic Psychology; D012727:Sex Characteristics; D012919:Social Behavior
D011619:Psychotropic Drugs; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D016291:Dizocilpine Maleate; D003913:Dextroamphetamine