期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 598, 期 1-3, 页码 43-50出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2008.09.006
关键词
GluR2; AMPA; Prefrontal cortex; Adult neurogenesis; Proton magnetic resonance spectroscopy; Antidepressant
资金
- Solvay Pharmaceuticals, Weesp, The Netherlands
We investigated the efficacy of SONU20176289, a member of a group of novel phenylpiperazine derivatives with a mixed dopamine D-2 receptor partial agonist and specific serotonin reuptake inhibitor (SSRI) activity, in a chronic stress model of depression in male tree shrews. Animals were subjected to a 7-day period of psychosocial stress before treatment for 28 days with SONU20176289 (6 mg/kg/day, p.o.), during which stress was maintained. Stress reduced the in vivo brain concentrations of N-acetyl-aspartate, total creatine, and choline-containing compounds, as measured by localized proton magnetic resonance spectroscopy. Post mortem analyses revealed a reduced adult dentate cell proliferation and a decreased GluR2 expression in the prefrontal cortex. All these alterations were prevented by concomitant administration of SONU20176289. The results provide further support to the concept that antidepressant treatments may act by normalizing disturbed neuroplasticity, and indicate that combining dopamine D-2 receptor agonism with SSRI activity may serve as an effective tool in the treatment of depressive/anxiety syndromes. (C) 2008 Elsevier B.V. All rights reserved.
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