title: Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice.
abstract: Extensive pharmacological studies have recently emerged indicating that group 2 metabotropic glutamate receptors (mGluRs) comprising mGluR2 and mGluR3 subtypes are associated with several neurological and psychiatric disorders. mGluR2 is widely distributed both presynaptically and postsynaptically in a variety of neuronal cells, but the physiological role of mGluR2 in brain function is poorly understood. This investigation involves a comprehensive behavioral analysis of mGluR2-/- knockout (KO) mice to explore the physiological role of mGluR2 in brain function. Although, under general observation, mGluR2-/- KO mice appeared to have no behavioral abnormalities, they exhibited several lines of behavioral alterations in the enforcing and defined behavioral tests. They showed a significant increase in locomotor sensitization and conditioned place preference in association with repeated cocaine administration, indicating that mGluR2 contributes to behavioral responses implicated in reinforcement and addiction of cocaine. Upon in vivo microdialysis analysis after cocaine administration, not only did extracellular levels of dopamine increase but also the response pattern of glutamate release markedly changed in the nucleus accumbens of mGluR2-/- KO mice. The mGluR2-/- KO mice also showed significant impairment in motor coordination in the accelerating rota-rod test and exhibited hyperlocomotion in novel environmental and stressful conditions, when assessed by the open-field and forced-swim tests. These results indicate that the inhibitory mGluR2 plays a pivotal role in synaptic regulation of glutamatergic transmission in the neural network.
authors.affiliation: Department of Biological Sciences, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Morishima
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Furuyashiki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuma
authors.forename: Shigetada
authors.initials: S
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
chemical_list: D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D018698:Glutamic Acid; D003042:Cocaine; D004298:Dopamine