polyFADO

In view of the limited efficacy and adverse side-effects of conventional antipsychotic (AP) treatment it is mandatory to develop alternative and adjuvant therapies. Evidence supports a central role of polyunsaturated fatty acids (PUFA) decrease in the etiology of some recurrent psychiatric disorders. Data obtained by the partners of this grant reveals that: 1) PUFA deficiency in a mouse model recapitulates some deficits of recurrent psychiatric disorders, directly related to alteration of dopamine D2 receptor (D2R)-dependent transmission; 2) membrane enrichment in PUFA considerably enhances ligand affinity to D2R. These data suggest that PUFA membrane enrichment could be an efficient strategy to enhance the efficacy of APs at the D2R. This hypothesis will be tested in the current project that will dissect out the effect of PUFAs on D2R pharmacology, dynamics, activation and signaling in vitro and in vivo using cutting-edge technologies.