TY - JOUR
T1 - M 4muscarinic receptor knockout mice display abnormal social behavior and decreased prepulse inhibition
AU - Koshimizu, Hisatsugu
AU - Leiter, Lorene M.
AU - Miyakawa, Tsuyoshi
N1 - Funding Information:
We thank Dr. Jürgen Wess (Molecular Signaling Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health) for providing the M4R KO mice and his critical reading of this manuscript. This work was supported by National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (TM) and Integrative Brain Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (TM).
PY - 2012
Y1 - 2012
N2 - Background: In the central nervous system (CNS), the muscarinic system plays key roles in learning and memory, as well as in the regulation of many sensory, motor, and autonomic processes, and is thought to be involved in the pathophysiology of several major diseases of the CNS, such as Alzheimer's disease, depression, and schizophrenia. Previous studies reveal that M 4muscarinic receptor knockout (M 4R KO) mice displayed an increase in basal locomotor activity, an increase in sensitivity to the prepulse inhibition (PPI)-disrupting effect of psychotomimetics, and normal basal PPI. However, other behaviorally significant roles of M 4R remain unclear. Results: In this study, to further investigate precise functional roles of M 4R in the CNS, M 4R KO mice were subjected to a battery of behavioral tests. M 4R KO mice showed no significant impairments in nociception, neuromuscular strength, or motor coordination/learning. In open field, light/dark transition, and social interaction tests, consistent with previous studies, M 4R KO mice displayed enhanced locomotor activity compared to their wild-type littermates. In the open field test, M 4R KO mice exhibited novelty-induced locomotor hyperactivity. In the social interaction test, contacts between pairs of M 4R KO mice lasted shorter than those of wild-type mice. In the sensorimotor gating test, M 4R KO mice showed a decrease in PPI, whereas in the startle response test, in contrast to a previous study, M 4R KO mice demonstrated normal startle response. M 4R KO mice also displayed normal performance in the Morris water maze test. Conclusions: These findings indicate that M 4R is involved in regulation of locomotor activity, social behavior, and sensorimotor gating in mice. Together with decreased PPI, abnormal social behavior, which was newly identified in the present study, may represent a behavioral abnormality related to psychiatric disorders including schizophrenia.
AB - Background: In the central nervous system (CNS), the muscarinic system plays key roles in learning and memory, as well as in the regulation of many sensory, motor, and autonomic processes, and is thought to be involved in the pathophysiology of several major diseases of the CNS, such as Alzheimer's disease, depression, and schizophrenia. Previous studies reveal that M 4muscarinic receptor knockout (M 4R KO) mice displayed an increase in basal locomotor activity, an increase in sensitivity to the prepulse inhibition (PPI)-disrupting effect of psychotomimetics, and normal basal PPI. However, other behaviorally significant roles of M 4R remain unclear. Results: In this study, to further investigate precise functional roles of M 4R in the CNS, M 4R KO mice were subjected to a battery of behavioral tests. M 4R KO mice showed no significant impairments in nociception, neuromuscular strength, or motor coordination/learning. In open field, light/dark transition, and social interaction tests, consistent with previous studies, M 4R KO mice displayed enhanced locomotor activity compared to their wild-type littermates. In the open field test, M 4R KO mice exhibited novelty-induced locomotor hyperactivity. In the social interaction test, contacts between pairs of M 4R KO mice lasted shorter than those of wild-type mice. In the sensorimotor gating test, M 4R KO mice showed a decrease in PPI, whereas in the startle response test, in contrast to a previous study, M 4R KO mice demonstrated normal startle response. M 4R KO mice also displayed normal performance in the Morris water maze test. Conclusions: These findings indicate that M 4R is involved in regulation of locomotor activity, social behavior, and sensorimotor gating in mice. Together with decreased PPI, abnormal social behavior, which was newly identified in the present study, may represent a behavioral abnormality related to psychiatric disorders including schizophrenia.
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U2 - 10.1186/1756-6606-5-10
DO - 10.1186/1756-6606-5-10
M3 - Article
C2 - 22463818
AN - SCOPUS:84859112623
SN - 1756-6606
VL - 5
JO - Molecular brain
JF - Molecular brain
IS - 1
M1 - 10
ER -