Co-administration of a D-amino acid oxidase inhibitor potentiates the efficacy of D-serine in attenuating prepulse inhibition deficits after administration of dizocilpine.
Biol Psychiatry
; 65(12): 1103-6, 2009 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-19217074
ABSTRACT
BACKGROUND:
D-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.METHODS:
Vehicle 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.RESULTS:
Coadministration 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.CONCLUSIONS:
These 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Serina
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Reflejo de Sobresalto
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Maleato de Dizocilpina
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Antagonistas de Aminoácidos Excitadores
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Inhibidores Enzimáticos
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Aminoácido Oxidorreductasas
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Isoxazoles
Idioma:
En
Revista:
Biol Psychiatry
Año:
2009
Tipo del documento:
Article
País de afiliación:
Japón