Reward-processing impairment is a common symptomatic dimension of several psychiatric disorders. However, whether the underlying pathological mechanisms are common is unknown. Herein, we asked if the decrease in the n-3 Polyunsaturated Fatty Acids (PUFAs) lipid species, consistently described in these pathologies, could underlie reward-processing deficits. We show that reduced n-3 PUFA biostatus in mice leads to selective motivational deficits. Electrophysiological recordings revealed increased collateral inhibition of dopamine D2 receptor (D2R)-expressing medium spiny neurons (iMSNs) onto dopamine D1 receptor-expressing (d)MSNs in the nucleus accumbens, a main brain region for the modulation of motivation. Strikingly, transgenically preventing n-3 PUFA deficiency selectively in D2R-expressing neurons normalizes MSNs collateral inhibition and enhances motivation. These results constitute the first demonstration of a causal link between a behavioral deficit and n-3 PUFA decrease in a discrete neuronal population and suggest that lower n-3 PUFA biostatus in psychopathologies could participate to the etiology of reward-related symptoms.
Ducrocq, Fabien and Walle, Roman and Contini, Andrea and Oummadi, Asma and Caraballo, Baptiste and van der Veldt, Suzanne and Boyer, Marie-Lou and Aby, Frank and Tolentino-Cortez, Tarson and Helbling, Jean-Christophe and Martine, Lucy and Grégoire, Stéphane and Cabaret, Stéphanie and Vancassel, Sylvie and Layé, Sophie and Kang, Jing Xuan and Fioramonti, Xavier and Berdeaux, Olivier and Barreda-Gómez, Gabriel and Masson, Elodie and Ferreira, Guillaume and Ma, David W. L. and Bosch-Bouju, Clémentine and De Smedt-Peyrusse, Véronique and Trifilieff, Pierre, Causal Link between n-3 Polyunsaturated Fatty Acid Deficiency and Motivation Deficits (May 3, 2019). Available at SSRN: https://ssrn.com/abstract=3382436 or http://dx.doi.org/10.2139/ssrn.3382436
This version of the paper has not been formally peer reviewed.
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