title: Splenectomy modifies hyperactive states of the dopaminergic system induced by morphine in C57BL/6J-bg(J)/bg(J) (beige-J) mice.
abstract: Genetic factors affect the locomotor activity induced by morphine, which mainly depends on the activation of dopaminergic systems, and morphine has distinct pharmacological activities in C57BL/6J-bg(J)bg(J) (beige-J) mice, which have genetic deficiencies in immunological function. We previously showed that beige-J mice exhibited greater locomotor activity and dopamine turnover, whereas splenectomy reduced this hyperlocomotion and dopamine turnover, which suggests that beige-J mice could be an experimental animal model for investigating hyperactivation of the dopaminergic system, and that the spleen may contribute to the susceptibility to activation of the dopaminergic system. Furthermore, morphine can induce hyperlocomotion mediated by activation of the dopaminergic system. Therefore, we examined the effects of splenectomy on the hyperlocomotion and regulation of the dopaminergic system induced by morphine in beige-J mice. Morphine induced hyperlocomotion, which was accompanied by activation of the dopaminergic system, in beige-J mice. Furthermore, splenectomy enhanced the hyperlocomotion and activation of the mesolimbic dopaminergic system induced by morphine in beige-J mice. Our findings indicate that substances originating from the spleen may regulate both spontaneous activation of the mesolimbic dopaminergic system and the µ-opioidergic system-mediated activation of the mesolimbic dopaminergic system by morphine through different modes of action. These results imply that beige-J mice could be a practical animal model for investigating the interactions between immune-modulation and the µ-opioidergic system and/or dopaminergic system.
authors.affiliation: Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Funada
authors.affiliation: Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.affiliation: Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuda
authors.affiliation: Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Komiya
authors.affiliation: Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Shimizu
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Kamei
authors.affiliation: Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. Electronic address: suzuki@hoshi.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D004298:Dopamine / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology; D006948:Hyperkinesis / Q000503:physiopathology; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology*; D013156:Splenectomy / Q000009:adverse effects
chemical_list: D009020:Morphine; D004298:Dopamine
keywords: Beige-J mice; Dopamine; Hyperlocomotion; Morphine; Splenectomy