The crosstalk between 5-HT_2AR and mGluR2 in schizophrenia

Schizophrenia is a severe brain disorder that usually produces a lifetime of disability. First generation or typical antipsychotics such as haloperidol and second generation or atypical antipsychotics such as clozapine and risperidone remain the current standard for schizophrenia treatment. In some patients with schizophrenia, antipsychotics produce complete remission of positive symptoms, such as hallucinations and delusions. However, antipsychotic drugs are ineffective against cognitive deficits and indeed treated schizophrenia patients have small improvements or even deterioration in several cognitive domains. This underlines the need for novel and more efficient therapeutic targets for schizophrenia treatment. Serotonin and glutamate have been identified as key parts of two neurotransmitter systems involved in fundamental brain processes. Serotonin (or 5-hydroxytryptamine) 5-HT_2A receptor (5-HT_2AR) and metabotropic glutamate 2 receptor (mGluR2) are G protein-coupled receptors (GPCRs) that interact at epigenetic and functional levels. These two receptors can form GPCR heteromeric complexes through which their pharmacology, function and trafficking becomes affected. Here we review past and current research on the 5-HT_2AR-mGluR2 heterocomplex and its potential implication in schizophrenia and antipsychotic drug action. This article is part of the Special Issue on "The receptor-receptor interaction as a new target for therapy".