کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6229175 | 1276601 | 2009 | 4 صفحه PDF | دانلود رایگان |

BackgroundD-Serine, an endogenous agonist of the N-methyl-D-aspartate (NMDA) receptors, is effective in the treatment of schizophrenia. However, orally administered D-serine is metabolized substantially by D-amino acid oxidase (DAAO), diminishing its oral bioavailability. In this study, we examined the effects of oral D-serine administration with or without a DAAO inhibitor, 5-chloro-benzo[d]isoxazol-3-ol (CBIO), on the prepulse inhibition (PPI) deficits after administration of the NMDA receptor antagonist dizocilpine.MethodsVehicle or D-serine (30, 300, or 900 mg/kg) with or without CBIO (30 mg/kg) was orally administered to mice 1 hour before administration of dizocilpine (.1 mg/kg), and then the PPI of the acoustic startle response was measured. We measured the extracellular levels of D-serine in the frontal cortex after oral administration of D-serine with or without CBIO.ResultsCoadministration of CBIO with D-serine (30 mg/kg), but not D-serine (30 mg/kg) alone, significantly attenuated dizocilpine-induced PPI deficits. Furthermore, coadministration of CBIO significantly increased the extracellular levels of D-serine in the frontal cortex after administration of D-serine.ConclusionsThese findings suggest that coadministration of CBIO significantly enhanced the efficacy of D-serine in attenuating PPI deficits by administration of dizocilpine. Therefore, coadministration of D-serine and a DAAO inhibitor has therapeutic potential for the treatment of schizophrenia.
Journal: Biological Psychiatry - Volume 65, Issue 12, 15 June 2009, Pages 1103-1106