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: Kristian Liaury, Tsuyoshi Miyaoka, Toshiko Tsumori, Motohide Furuya, Sadayuki Hashioka, Rei Wake, Keiko Tsuchie, Michiyo Fukushima, Erlyn Limoa, Andi Jayalangkara Tanra, Jun Horiguchi
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 50 Pg. 184-90 (Apr 03 2014) ISSN: 1878-4216 [Electronic] England
• PMID: 24389395 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013. Published by Elsevier Inc.

Chemical References

• Antipsychotic Agents
• CD11b Antigen
• Minocycline

Topics

• Animals
• Antipsychotic Agents (pharmacology, therapeutic use)
• CD11b Antigen (biosynthesis)
• Dentate Gyrus (drug effects)
• Disease Models, Animal
• Hyperbilirubinemia (complications, drug therapy, psychology)
• Male
• Microglia (drug effects, metabolism)
• Minocycline (pharmacology, therapeutic use)
• Rats
• Rats, Gunn
• Rats, Wistar
• Recognition, Psychology (drug effects)
• Schizophrenia (chemically induced, complications, drug therapy)
• Schizophrenic Psychology
• Sensory Gating (drug effects)