Group 1 metabotropic glutamate receptors and schizophrenia

Abstract

Schizophrenia is a prevalent neuropsychiatric disorder associated with perturbations in medial prefrontal cortex (PFC) excitability and connectivity. As such, research into the neurobiology of schizophrenia and related psychotic disorders has focused on understanding the possible role played by the major excitatory neurotransmitter glutamate in mediating the cognitive and psychosocial impairments characteristic of this disease. Historically, the ionotropic NMDA glutamate receptor has received the greatest experimental attention in this regard. However, converging data point to Group 1 metabotropic glutamate receptors (mGluRs), as well as the Group 1 mGluR scaffolding protein Homer, as critical for normal psychomotor and cognitive function. Moreover, data derived primarily from behavioral pharmacological and genetic studies conducted in animal models of psychosis, suggest that dysregulation of Group 1 mGluR signaling may contribute to anomalies in neuronal excitation putatively underpinning the manifestation of cognitive abnormalities and psychotic-like behavior. These data implicate targeting Group 1 mGluRs as viable pharmacotherapeutic strategies for the treatment of schizophrenia and related disorders. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.