title: Minocycline improves recognition memory and attenuates microglial activation in Gunn rat: a possible hyperbilirubinemia-induced animal model of schizophrenia.
abstract: BACKGROUND
  Accumulating evidence indicates that neuroinflammation plays a significant role in the pathophysiology of schizophrenia. We previously reported evidence of schizophrenia-like behaviors and microglial activation in Gunn rats. We concluded that the Gunn rat, which exhibits a high concentration of unconjugated bilirubin, may be useful as an animal model of schizophrenia. On the other hand, there have been numerous reports that minocycline is effective in treating schizophrenia.
  
  
  METHODS
  In the present study, we investigated the effects of minocycline on performance of behavioral tests (prepulse inhibition (PPI) and novel object recognition test (NORT)) after animals received either 40mg/kg/d of minocycline or vehicle by intraperitoneal (i.p.) injection for 14 consecutive days. Furthermore, we examined the effects of minocycline on microglial activation in the hippocampal dentate gyrus of Gunn rats and Wistar rats.
  
  
  RESULTS
  We found that administration of minocycline for 14days significantly increased the exploratory preference in retention sessions and tended to improve the PPI deficits in Gunn rats. Immunohistochemistry analysis revealed that microglial cells in the minocycline-treated Gunn rat group showed less expression of CD11b compared to vehicle-treated Gunn and Wistar groups.
  
  
  CONCLUSIONS
  Our findings suggest that minocycline improves recognition memory and attenuates microglial activation in the hippocampal dentate gyrus of Gunn rats. Therefore, minocycline may be a potential therapeutic drug for schizophrenia.
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan; Department of Psychiatry, Hasanuddin University Faculty of Medicine, Jl. Perintis Kemerdekaan Km. 10, Makassar 90245, South Sulawesi, Indonesia. Electronic address: krizbox@hotmail.com.
authors.forename: Kristian
authors.initials: K
authors.lastname: Liaury
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: miyanyan@med.shimane-u.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyaoka
authors.affiliation: Department of Anatomy Morphological Neuroscience, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan; Department of Nursing, Faculty of Health and Welfare, Prefectural University of Hiroshima, 1-1 Gakuen-cho, Mihara 723-0053, Japan. Electronic address: t-tsumori@pu-hiroshima.ac.jp.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tsumori
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: pancho@med.shimane-u.ac.jp.
authors.forename: Motohide
authors.initials: M
authors.lastname: Furuya
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: hashioka@med.shimane-u.ac.jp.
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Hashioka
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: rei@med.shimane-u.ac.jp.
authors.forename: Rei
authors.initials: R
authors.lastname: Wake
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: keits@med.shimane-u.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Tsuchie
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: mtaki@med.shimane-u.ac.jp.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Fukushima
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan; Department of Psychiatry, Hasanuddin University Faculty of Medicine, Jl. Perintis Kemerdekaan Km. 10, Makassar 90245, South Sulawesi, Indonesia. Electronic address: erlynliem@yahoo.com.
authors.forename: Erlyn
authors.initials: E
authors.lastname: Limoa
authors.affiliation: Department of Psychiatry, Hasanuddin University Faculty of Medicine, Jl. Perintis Kemerdekaan Km. 10, Makassar 90245, South Sulawesi, Indonesia. Electronic address: ajtanra@yahoo.com.
authors.forename: Andi Jayalangkara
authors.initials: AJ
authors.lastname: Tanra
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. Electronic address: jhorigu@med.shimane-u.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Horiguchi
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D039481:CD11b Antigen / Q000096:biosynthesis; D018891:Dentate Gyrus / Q000187:drug effects; D004195:Disease Models, Animal; D006932:Hyperbilirubinemia / Q000150:complications / Q000188:drug therapy / Q000523:psychology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011911:Rats, Gunn; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D012559:Schizophrenia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D055139:Sensory Gating / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D039481:CD11b Antigen; D008911:Minocycline
keywords: Activated microglia; Behavioral test; Gunn rat; Minocycline; Schizophrenia; Unconjugated bilirubin