Dopamine D2 receptor as a novel target molecule for heart-type fatty acid binding protein

Essential roles of long-chain polyunsaturated fatty acids (LCPUFAs) have been documented in higher brain functions including emotion, learning and memory. Several clinical studies indicate that oral administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can improve emotional and cognitive dysfunctions in schizophrenic patients. Likewise, arachidonic acid supplementation can improve cognitive dysfunction seen in human neurodegenerative disorders such as Alzheimer's disease. Since LCPUFAs are insoluble in an aqueous cellular environment, fatty acid binding proteins (FABPs) are essential to function as intracellular transport of LCPUFAs to appropriate intracellular compartments. Of various FABPs, heart-type fatty acid binding protein (H-FABP, FABP3) is highly expressed in neurons of mature brain. We previously demonstrated that H-FABP is associated with dopamine D2 receptor long isoform (D2LR) in vitro. Furthermore, we demonstrated that H-FABP knockout mice exhibit dopamine D2 receptor dysfunction. These results indicate that administration of LCPUFAs regulates dopamine D2 receptor functions through H-FABP in the brain.