The dopamine mesocorticolimbic pathway is affected by deficiency in n-3 polyunsaturated fatty acids
The American Journal of Clinical Nutrition. 2002-04-01; 75(4): 662-667
DOI: 10.1093/ajcn/75.4.662
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1. Am J Clin Nutr. 2002 Apr;75(4):662-7. doi: 10.1093/ajcn/75.4.662.
The dopamine mesocorticolimbic pathway is affected by deficiency in n-3
polyunsaturated fatty acids.
Zimmer L(1), Vancassel S, Cantagrel S, Breton P, Delamanche S, Guilloteau D,
Durand G, Chalon S.
Author information:
(1)INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique,
Université François Rabelais, Tours, France.
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
transporter(2) and dopamine D(2) 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 transporter(2) was lower in both cerebral areas in n-3
PUFA-deficient rats than in control rats, whereas the mRNA expression of D(2)
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.
DOI: 10.1093/ajcn/75.4.662
PMID: 11916751 [Indexed for MEDLINE]