Schizophrenia: Metabotropic glutamate receptors trigger nitric oxide signaling pathway

Abstract

ABSTRACT

Schizophrenia is a highly prevalent mental disorder, triggered by biopsychosocial factors, associated with biological factors - physiological and genetic, which affects the functional ability of patients. Its signs and symptoms are divided into three groups: positive, negative and cognitive. The traditional antipsychotic drugs, which act directly into the dopaminergic pathway, have demonstrated inefficiency in relief the last two. Evidence report the strict relationship between the dopaminergic neurotransmission and its regulation by the glutamatergic one in several brain regions such as prefrontal cortex and hippocampus, by either ionotropic or metabotropic receptors. Metabotropic receptors show higher specificity than ionotropic receptors probably because their distribution in the brain is more concentrated in specific areas and also because they have modulatory effect over ionotropic receptors. Additionally, several studies have contributed to establish a relationship between glutamatergic neurotransmission and the nitric oxide in the physiopathology of schizophrenia. The increased activation of the NMDA receptors influence the symptoms of schizophrenia as they activate NO/cGMP/PKC signaling pathway. However, the studies are quite different in relation to the role of the NO in the brain mechanisms involved in this neuropathology. Pharmacological and non pharmacological experimental models have been used to study the brain alterations that occur in schizophrenia and might contribute to clarify the mechanisms involved as well as to identify new therapeutic targets to the treatment of its symptoms.