Deficits in social behavior and sensorimotor gating in mice lacking phospholipase Cbeta1.
Abnormal phospholipid metabolism has been implicated in the pathogenesis of schizophrenia, and it was reported that phospholipase C (PLC) beta1 is reduced in specific brain areas of patients with schizophrenia. However, the causal relationship of the PLCbeta1 gene with behavioral symptoms of schizophrenia remains unclear. To address this issue, we have examined the mutant mice lacking PLCbeta1 for schizophrenia-related phenotypes by performing various behavioral tests, including general locomotor activity, sensorimotor gating, social behaviors, and learning and memory. Phospholipase C beta1 knockout mice showed hyperactivities in an open field. They showed impaired prepulse inhibition of acoustic startle response, which was ameliorated by a systemic administration of an antipsychotic D2-receptor antagonist, haloperidol. In addition, they showed abnormal social behaviors, such as lack of barbering behavior, socially recessive trait and lack of nesting behavior. Furthermore, they showed impaired performance in the delayed-non-match-to-sample T-maze test. The present results show that the PLCbeta1 mutant mice share some of the behavioral abnormalities that have been reported in patients with schizophrenia. Thus, the PLCbeta1-linked signaling pathways may be involved in the neural system whose function is disrupted in the pathogenesis of schizophrenia.
Koh
H-Y
HY
Center for Neural Science, Korea Institute of Science and Technology, Seoul, Korea.
Kim
D
D
Lee
J
J
Lee
S
S
Shin
H-S
HS
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001143:Arousal / Q000187:drug effects / Q000235:genetics*; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D005808:Genes, Recessive; D006120:Grooming / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D011939:Mental Recall / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008957:Models, Genetic; D009425:Nesting Behavior / Q000502:physiology; D054799:Phospholipase C beta / Q000235:genetics*; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D012919:Social Behavior
D014150:Antipsychotic Agents; D054799:Phospholipase C beta; C518034:Plcb1 protein, mouse; D006220:Haloperidol