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The dopamine mesocorticolimbic pathway is affected by deficiency in n-3 polyunsaturated fatty acids^1,2,3

¹ From INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, Université François Rabelais, Tours, France (LZ, SC, DG, and SC); the INRA, Laboratoire de Nutrition et Sécurité Alimentaire, Jouy-en-Josas, France (SV and GD); and the Centre d'Etudes du Bouchet, Vert-le-Petit, France (PB and SD).

Background: Several findings in humans support the hypothesis of links between n-3 polyunsaturated fatty acid (PUFA) status and psychiatric diseases.

Objective: The involvement of PUFAs in central nervous system function can be assessed with the use of dietary manipulation in animal models. We studied the effects of chronic dietary n-3 PUFA deficiency on mesocorticolimbic dopamine neurotransmission in rats.

Design: Using dual-probe microdialysis, we analyzed dopamine release under amphetamine stimulation simultaneously in the frontal cortex and the nucleus accumbens. The messenger RNA (mRNA) expression of vesicular monoamine transporter₂ and dopamine D₂ receptor was studied with the use of in situ hybridization. The protein expression of the synthesis-limiting enzyme tyrosine 3-monooxygenase (tyrosine 3-hydroxylase) was studied with the use of immunocytochemistry.

Results: Dopamine release was significantly lower in both cerebral areas in n-3 PUFA–deficient rats than in control rats, but this effect was abolished in the frontal cortex and reversed in the nucleus accumbens by reserpine pretreatment, which depletes the dopamine vesicular storage pool. The mRNA expression of vesicular monoamine transporter₂ was lower in both cerebral areas in n-3 PUFA–deficient rats than in control rats, whereas the mRNA expression of D₂ receptor was lower in the frontal cortex and higher in the nucleus accumbens in n-3 PUFA–deficient rats than in control rats. Finally, tyrosine 3-monooxygenase immunoreactivity was higher in the ventral tegmental area in n-3 PUFA–deficient rats than in control rats.

Conclusions: Our results suggest that the mesolimbic dopamine pathway is more active whereas the mesocortical pathway is less active in n-3 PUFA–deficient rats than in control rats. This provides new neurochemical evidence supporting the effects of n-3 PUFA deficiency on behavior.

Key Words: Dopamine • mesocorticolimbic pathway • frontal cortex • microdialysis • n-3 polyunsaturated fatty acids • nucleus accumbens • rats

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