MODULATION OF MGLUR SIGNALING AND METHODS OF USE IN NEUROLOGICAL AND PSYCHIATRIC DISEASES

摘要

In accordance with the present invention there are provided methods of modulating the activity of metabotropic glutamate receptors (mGluRs) and/or dopamine receptors involving inhibiting the activity of a prolyl isomerase. Further provided are methods of identifying a test compound that inhibits Pin 1 activity on group 1 metabotropic glutamate receptors (mGluR). Also provided are methods of decreasing dopamine signaling in a subject having enhanced dopamine signaling including administering a prolyl isomerase inhibitor to the subject, wherein the subject has a drug addiction, inflammatory pain, schizophrenia, or a movement disorder. Also provided are methods of treating a disease or disorder related to enhanced dopamine signaling or an mGluR-related disorder. Finally, there are provided transgenic animals having variant mGluRs which exhibit altered Pinl or Homer binding properties.