title: Antipsychotic treatment modulates glutamate transport and NMDA receptor expression.
abstract: Schizophrenia patients often suffer from treatment-resistant cognitive and negative symptoms, both of which are influenced by glutamate neurotransmission. Innovative therapeutic strategies such as agonists at metabotropic glutamate receptors or glycin reuptake inhibitors try to modulate the brain's glutamate network. Interactions of amino acids with monoamines have been described on several levels, and first- and second-generation antipsychotic agents (FGAs, SGAs) are known to exert modulatory effects on the glutamatergic system. This review summarizes the current knowledge on effects of FGAs and SGAs on glutamate transport and receptor expression derived from pharmacological studies. Such studies serve as a control for molecular findings in schizophrenia brain tissue and are clinically relevant. Moreover, they may validate animal models for psychosis, foster basic research on antipsychotic substances and finally lead to a better understanding of how monoaminergic and amino acid neurotransmissions are intertwined. In the light of these results, important differences dependent on antipsychotic substances, dosage and duration of treatment became obvious. While some post-mortem findings might be confounded with multifold drug effects, others are unlikely to be influenced by antipsychotic treatment and could represent important markers of schizophrenia pathophysiology. In similarity to the convergence of toxic and psychotomimetic effects of dopaminergic, serotonergic and anti-glutamatergic substances, the therapeutic mechanisms of SGAs might merge on a yet to be defined molecular level. In particular, serotonergic effects of SGAs, such as an agonism at 5HT1A receptors, represent important targets for further clinical research.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, P.O. Box 12 21 20, 68072, Mannheim, Germany, mathias.zink@zi-mannheim.de.
authors.forename: Mathias
authors.initials: M
authors.lastname: Zink
authors.forename: Susanne
authors.initials: S
authors.lastname: Englisch
authors.forename: Andrea
authors.initials: A
authors.lastname: Schmitt
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D027322:Amino Acid Transport System X-AG; D014150:Antipsychotic Agents; D016194:Receptors, N-Methyl-D-Aspartate