Causal Link between n-3 Polyunsaturated Fatty Acid Deficiency and Motivation Deficits.
Cell Metabolism. 2020-04-01; 31(4): 755-772.e7
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Ducrocq F(1), Walle R(2), Contini A(2), Oummadi A(2), Caraballo B(2), van der Veldt S(2), Boyer ML(2), Aby F(2), Tolentino-Cortez T(3), Helbling JC(2), Martine L(4), Grégoire S(4), Cabaret S(4), Vancassel S(2), Layé S(2), Kang JX(5), Fioramonti X(2), Berdeaux O(4), Barreda-Gómez G(3), Masson E(4), Ferreira G(2), Ma DWL(6), Bosch-Bouju C(2), De Smedt-Peyrusse V(2), Trifilieff P(7).
(1)Université Bordeaux, INRAE, Bordeaux INP, NutriNeuro, 33000, Bordeaux, France. Electronic address: .
(2)Université Bordeaux, INRAE, Bordeaux INP, NutriNeuro, 33000, Bordeaux, France.
(3)Research Department, IMG Pharma Biotech S.L., BIC Bizkaia (612), 48160 Derio, Spain.
(4)Centre des Sciences du Goût et de l’Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, 21000 Dijon, France.
(5)Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
(6)Department of Human Health and Nutritional Sciences, University of Guelph, 50 Stone Road E., Guelph, ON N1G2W1, Canada.
(7)Université Bordeaux, INRAE, Bordeaux INP, NutriNeuro, 33000, Bordeaux, France. Electronic address: .
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 acid (PUFA) 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 impairments. Electrophysiological recordings revealed increased collateral inhibition of dopamine D2 receptor-expressing medium spiny neurons (D2-MSNs) onto dopamine D1 receptor-expressing MSNs in the nucleus accumbens, a main brain region for the modulation of motivation. Strikingly, transgenically preventing n-3 PUFA deficiency selectively in D2-expressing neurons normalizes MSN 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 in the etiology of reward-related symptoms.