ArticleTranslational psychiatry2012
NAAG peptidase inhibitors block cognitive deficit induced by MK-801 and motor activation induced by d-amphetamine in animal models of schizophrenia.
Article in Translational psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- Post-methamphetamine working memory decline predicts relapse vulnerability in rats and is rescued by mGlu3 receptor activation.Psychopharmacology · 2026Article
- Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Mass spectrometry-guided discovery of novel GCPII inhibitor scaffolds.Frontiers in pharmacology · 2025Article
- Effects of systemic pretreatment with the NAALADase inhibitor 2-PMPA on oral methamphetamine reinforcement in C57BL/6J mice.Frontiers in psychiatry · 2024Article
- Dendrimer-enabled targeted delivery attenuates glutamate excitotoxicity and improves motor function in a rabbit model of cerebral palsy.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Metabotropic glutamate receptor 3 as a potential therapeutic target for psychiatric and neurological disorders.Pharmacology, biochemistry, and behavior · 2022Review
- Inhibition of glutamate-carboxypeptidase-II in dorsolateral prefrontal cortex: potential therapeutic target for neuroinflammatory cognitive disorders.Molecular psychiatry · 2022Article
- Group II Metabotropic Glutamate Receptors Reduce Apoptosis and Regulate BDNF and GDNF Levels in Hypoxic-Ischemic Injury in Neonatal Rats.International journal of molecular sciences · 2022Article
- Metabotropic Glutamate Receptors As Emerging Targets for the Treatment of Schizophrenia.Molecular pharmacology · 2022Review
- Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects.Frontiers in chemistry · 2022Review
- Dendrimer-2PMPA selectively blocks upregulated microglial GCPII activity and improves cognition in a mouse model of multiple sclerosis.Nanotheranostics · 2022Article
- The NMDA receptor antagonist MK-801 fails to impair long-term recognition memory in mice when the state-dependency of memory is controlled.Neurobiology of learning and memory · 2019Article
- A role for N-acetylaspartylglutamate (NAAG) and mGluR3 in cognition.Neurobiology of learning and memory · 2019Review
- Magnetic Resonance Spectroscopy in Schizophrenia: Evidence for Glutamatergic Dysfunction and Impaired Energy Metabolism.Neurochemical research · 2019Review
- Synaptic NMDA Receptor Activation Induces Ubiquitination and Degradation of STEPMolecular neurobiology · 2018Article
- Inhibition of STEPMolecular psychiatry · 2018Article
- Striatal N-Acetylaspartate Synthetase Shati/Nat8l Regulates Depression-Like Behaviors via mGluR3-Mediated Serotonergic Suppression in Mice.The international journal of neuropsychopharmacology · 2017Article
- NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer's, and Ethanol Intoxication.Neurochemical research · 2017Article
- A role for the locus coeruleus in the analgesic efficacy of N-acetylaspartylglutamate peptidase (GCPII) inhibitors ZJ43 and 2-PMPA.Molecular pain · 2017Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
The most widely validated animal models of the positive, negative and cognitive symptoms of schizophrenia involve administration of d-amphetamine or the open channel NMDA receptor blockers, dizocilpine (MK-801), phencyclidine (PCP) and ketamine. The drug ZJ43 potently inhibits glutamate carboxypeptidase II (GCPII), an enzyme that inactivates the peptide transmitter N-acetylaspartylglutamate (NAAG) and reduces positive and negative behaviors induced by PCP in several of these models. NAAG is an agonist at the metabotropic glutamate receptor 3 (mGluR3). Polymorphisms in this receptor have been associated with expression of schizophrenia. This study aimed to determine whether two different NAAG peptidase inhibitors are effective in dopamine models, whether their efficacy was eliminated in GCPII knockout mice and whether the efficacy of these inhibitors extended to MK-801-induced cognitive deficits as assessed using the novel object recognition test. ZJ43 blocked motor activation when given before or after d-amphetamine treatment. (R,S)-2-phosphono-methylpentanedioic acid (2-PMPA), another potent NAAG peptidase inhibitor, also reduced motor activation induced by PCP or d-amphetamine. 2-PMPA was not effective in GCPII knockout mice. ZJ43 and 2-PMPA also blocked MK-801-induced deficits in novel object recognition when given before, but not after, the acquisition trial. The group II mGluR antagonist LY341495 blocked the effects of NAAG peptidase inhibition in these studies. 2-PMPA was more potent than ZJ43 in a test of NAAG peptidase inhibition in vivo. By bridging the dopamine and glutamate theories of schizophrenia with two structurally different NAAG peptidase inhibitors and demonstrating their efficacy in blocking MK-801-induced memory deficits, these data advance the concept that NAAG peptidase inhibition represents a potentially novel antipsychotic therapy.
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