Translational studies of group II metabotropic glutamate receptors (mGluR2, mGluR3) and their role in schizophrenia

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All current drugs used to treat schizophrenia work by blocking actions of a brain chemical transmitter called dopamine. Unfortunately these drugs are not very effective and have many side-effects. Recent research has suggested that another transmitter, glutamate, is also important in schizophrenia, and that drugs working on this system may be better. Glutamate acts by binding to molecules called receptors. One subtype of these is called group II metabotropic glutamate receptors (mGluRs), and these are of great interest because last year a drug which acts on these receptors was shown to be effective (and free of major side effects) in treatment of schizophrenia - the first ever non-dopamine drug to succeed in the illness. We have been working on group II mGluRs for several years, and this application seeks to build upon our existing knowledge and expertise to disover more about how these receptors work and so help make better drugs for schizophrenia. To do this, we will use genetic and molecular methods, investigate how brain cells work in the absence of these receptors, and study the receptors in the brains of people who had the illness. In line with this funding scheme, the work will be done jointly and in active collaboration with colleagues at GlaxoSmithKline in Harlow.