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Previous studies reveal that M<jats:sub>4<\/jats:sub>muscarinic receptor knockout (M<jats:sub>4<\/jats:sub>R 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<jats:sub>4<\/jats:sub>R remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, to further investigate precise functional roles of M<jats:sub>4<\/jats:sub>R in the CNS, M<jats:sub>4<\/jats:sub>R KO mice were subjected to a battery of behavioral tests. M<jats:sub>4<\/jats:sub>R 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<jats:sub>4<\/jats:sub>R KO mice displayed enhanced locomotor activity compared to their wild-type littermates. In the open field test, M<jats:sub>4<\/jats:sub>R KO mice exhibited novelty-induced locomotor hyperactivity. In the social interaction test, contacts between pairs of M<jats:sub>4<\/jats:sub>R KO mice lasted shorter than those of wild-type mice. In the sensorimotor gating test, M<jats:sub>4<\/jats:sub>R KO mice showed a decrease in PPI, whereas in the startle response test, in contrast to a previous study, M<jats:sub>4<\/jats:sub>R KO mice demonstrated normal startle response. M<jats:sub>4<\/jats:sub>R KO mice also displayed normal performance in the Morris water maze test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings indicate that M<jats:sub>4<\/jats:sub>R 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.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1756-6606-5-10","type":"journal-article","created":{"date-parts":[[2012,4,2]],"date-time":"2012-04-02T04:21:12Z","timestamp":1333340472000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["M4 muscarinic receptor knockout mice display abnormal social behavior and decreased prepulse inhibition"],"prefix":"10.1186","volume":"5","author":[{"given":"Hisatsugu","family":"Koshimizu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorene M","family":"Leiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Miyakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,4,2]]},"reference":[{"key":"156_CR1","unstructured":"Proceedings of the Sixth International Symposium on Subtypes of Muscarinic Receptors. 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