کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6265131 | 1614068 | 2011 | 5 صفحه PDF | دانلود رایگان |

Glutamate carboxypeptidase II (GCP II) is a glial enzyme responsible for the hydrolysis of N-acetylaspartylglutamate (NAAG) into glutamate and N-acetylaspartate (NAA). Abnormalities in glutamate neurotransmission are implicated in the pathophysiology of schizophrenia. In this study, we examined the effects of a novel, orally active GCP II inhibitor, 2-(3-mercaptopropyl)pentanedioic acid (2-MPPA), on the prepulse inhibition (PPI) deficits after administration of the N-methyl-d-aspartate (NMDA) receptor antagonist dizocilpine. Oral administration of 2-MPPA (10, 30 or 100Â mg/kg) significantly attenuated dizocilpine (0.1Â mg/kg)-induced PPI deficits in mice, in a dose dependent manner. Furthermore, the efficacy of 2-MPPA on dizocilpine-induced PPI deficits was significantly antagonized by pretreatment with the selective group II metabotropic glutamate receptor (mGluR) antagonist LY341495 (1.0Â mg/kg). In the same model, however, the selective group II mGluR agonist LY354740 (3, 10 or 30Â mg/kg) significantly attenuated dizocilpine-induced PPI deficits at only one dose and prepulse intensity. Our findings suggest that GCP II inhibition may be useful therapeutic strategy for schizophrenia. From a mechanistic perspective, while increased NAAG and activation of group II mGluRs may contribute to the therapeutic efficacy of 2-MPPA, it is likely that additional pharmacological activities are also involved.
Research HighlightsâºGlutamate carboxypeptidase II (GCP II) is an enzyme responsible for the hydrolysis of N-acetylaspartylglutamate. âº2-MPPA is an orally active GCP II inhibitor. âº2-MPPA attenuated dizocilpine-induced prepulse inhibition deficits in mice. âºGCP II inhibitors may be useful therapeutic drugs for schizophrenia.
Journal: Brain Research - Volume 1371, 31 January 2011, Pages 82-86