The role of N-methyl-d-aspartate receptors and metabotropic glutamate receptor 5 in the prepulse inhibition paradigms for studying schizophrenia: pharmacology, neurodevelopment, and genetics

Treatments for the positive and negative symptoms of schizophrenia have been explored for decades, but no completely successful therapy has been found as yet. Metabotropic glutamate receptor 5 (mGluR5), which potentiates N-methyl-d-aspartate receptors in brain regions implicated in schizophrenia, has become a novel drug target in the treatment of schizophrenia, especially for the mGluR5-positive allosteric modulators. Individuals with schizophrenia show deficits in prepulse inhibition (PPI), which is an operational measurement of sensorimotor gating. In this review, we focus on pharmacological, neurodevelopmental, and genetic animal models of disrupted PPI, with the aim of showing the potential role of mGluR5 in modulating the activity of N-methyl-d-aspartate receptors and their contributions toward the treatment of schizophrenia. As, the impairment of attentional modulation of PPI, but not that of baseline PPI, in individuals with schizophrenia is correlated with their symptom severity, this review also highlights that investigation of attentional modulation of PPI is critical for studying both cognitive impairments and glutamatergic dysfunctions of schizophrenia.