Modulation of CRF potentiation of NMDA receptor currents via CRF receptor 2

摘要

This invention pertains to the discovery that CRF increases NMDAR (N-methyl-D-aspartate receptor)-mediated currents at excitatory synapses onto a subset of dopamine cells in the ventral tegmental area (VTA) in the mammalian brain. This effect is not blocked by a CRF receptor 1 (CRF-R1) antagonist, but is blocked by a CRF receptor 2 (CRF-R2) antagonist. It was also discovered that an inhibitor of the CRF-binding protein (CRF-BP) blocks the effects of CRF, which indicates that CRF-BP, rather than inactivating “free” CRF, is necessary for CRF to potentiate NMDAR currents. Methods are provided that exploit this discovery to screen for modulators (upregulators or downregulators) of NMDA potentiation by CRF.