The dopamine mesocorticolimbic pathway is affected by deficiency in n-3 polyunsaturated fatty acids.
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.


METHODS
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.
Zimmer
Luc
L
INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, Université François Rabelais, Tours, France.
Vancassel
Sylvie
S
Cantagrel
Sylvain
S
Breton
Patrick
P
Delamanche
Séraphin
S
Guilloteau
Denis
D
Durand
Georges
G
Chalon
Sylvie
S
D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004032:Diet; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000172:deficiency*; D005260:Female; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D026901:Membrane Transport Proteins; D017551:Microdialysis; D009479:Neuropeptides; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D015259:Dopamine Agents; D005231:Fatty Acids, Unsaturated; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D000661:Amphetamine; D004298:Dopamine