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Psychopharmacology

, Volume 206, Issue 2, pp 215–222 | Cite as

Chronic treatment with AMPA receptor potentiator Org 26576 increases neuronal cell proliferation and survival in adult rodent hippocampus

  • Xiaowei W. Su
  • Xiao-Yuan Li
  • Mounira Banasr
  • Ja Wook Koo
  • Mohammed Shahid
  • Brian Henry
  • Ronald S. Duman
Original Investigation

Abstract

Rationale

Currently available antidepressants upregulate hippocampal neurogenesis and prefrontal gliogenesis after chronic administration, which could block or reverse the effects of stress. Allosteric α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiators (ARPs), which have novel targets compared to current antidepressants, have been shown to have antidepressant properties in neurogenic and behavioral models.

Objectives

This study analyzed the effect of the ARP Org 26576 on the proliferation, survival, and differentiation of neurons and glia in the hippocampus and prelimbic cortex of adult rats.

Materials and methods

Male Sprague-Dawley rats received acute (single day) or chronic (21 day) twice-daily intraperitoneal injections of Org 26576 (1–10 mg/kg). Bromodeoxyuridine (BrdU) immunohistochemistry was conducted 24 h or 28 days after the last drug injection for the analysis of cell proliferation or survival, respectively. Confocal immunofluorescence analysis was used to determine the phenotype of surviving cells.

Results

Acute administration of Org 26576 did not increase neuronal cell proliferation. However, chronic administration of Org 26576 increased progenitor cell proliferation in dentate gyrus (~40%) and in prelimbic cortex (~35%) at the 10-mg/kg dosage. Cells born in response to chronic Org 26576 in dentate gyrus exhibited increased rates of survival (~30%) with the majority of surviving cells expressing a neuronal phenotype.

Conclusion

Findings suggest that Org 26576 may have antidepressant properties, which may be attributed, in part, to upregulation of hippocampal neurogenesis and prelimbic cell proliferation.

Keywords

Antidepressant Gliogenesis Prefrontal cortex 

Notes

Acknowledgments

Funding was provided through a grant from Schering-Plough.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Xiaowei W. Su
    • 1
  • Xiao-Yuan Li
    • 1
  • Mounira Banasr
    • 1
  • Ja Wook Koo
    • 2
  • Mohammed Shahid
    • 3
  • Brian Henry
    • 3
  • Ronald S. Duman
    • 1
  1. 1.Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health CenterYale University School of MedicineNew HavenUSA
  2. 2.Department of PsychiatryMount Sinai School of MedicineNew York CityUSA
  3. 3.Department of PharmacologySchering-PloughLanarkshireUK

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