Disturbed Function of GABAergic Interneurons in Schizophrenia: Relevance for Medical Treatment?

J.      Genius; I.      Giegling; J.      Benninghoff; D.      Rujescu

Abstract

For decades treatment of schizophrenia was restricted to drugs, which mainly target positive symptoms by interfering with the dopaminergic neurotransmission.

Since a large body of experimental and clinical data implicate that schizophrenia may primarily be a consequence of an imbalance in the glutamatergic system, specifically the networks containing GABAergic interneurons (γ-amino butyric acid), new drugs modulating glutamatergic neurotransmission are being developed. Targeting this dysfunction may follow different strategies, including application of direct or indirect NMDA (N-methyl-D-aspartate) receptor agonists or drugs modulating the function of metabotropic glutamate receptors. Meanwhile, the first substances have proven to be effective in animal models of schizophrenia and now enter the stage of clinical trials. The most promising data have been obtained in studies employing agonists of the metabotropic glutamate receptor. A choice of these substances is presented in this review.

Keywords: Schizophrenia, Treatment, Glutamatergic system, NMDA receptor, Metabotropic Glutamate receptors, GABAergic interneurons, glutamatergic neurotransmission, "drugs modulating", metabotropic glutamate receptors, animal models