Hubert Milon

Effect of low intake of n−3 fatty acids during development on brain phospholipid fatty acid composition and exploratory behavior in rats

The effect of dietary restriction of n−3 fatty acids during development on brain phospholipid fatty acid composition and exploratory behavior has been studied in male Sprague Dawley rats. Female rats were fed semipurified diets containing either 5.5% safflower oil or 6% soybean oil for 6 wk prior to mating and throughout gestation and lactation. Control rats were maintained on laboratory chow. The male pups were weaned to the diets of the dams except for one group which was switched from safflower to soybean oil at weaning. Behavioral studies and brain phospholipid analyses were conducted at 16–18 wk of age. Rats fed safflower oil showed significantly lower levels of 22∶6n−3 in phospholipids of synaptic membranes and myelin than rats fed soybean oil or chow. The decrease in 22∶6n−3 was compensated for by an increase in 22∶5n−6, the total content of polyunsaturated fatty acids remaining approximately constant. The brain phospholipid fatty acid composition of rats switched from safflower to soybean oil at weaning was similar to that of rats fed soybean oil throughout the experiment. There was no difference in spontaneous locomotor activity among the different dietary groups. However, rats raised on safflower oil displayed a significantly lower exploratory activity (horizontal movements and rearings) in a novel environment than rats fed soybean oil or chow. In contrast to the brain phospholipid fatty acid composition, there was no recovery of exploratory behavior in rats raised on safflower oil and switched to soybean oil at weaning suggesting a specific requirement of n−3 fatty acids during development.

Serotonin and dopamine afferents to the rat locus coeruleus: a biochemical study after lesioning of the ventral mesencephalic tegmental-A10 region and the raphe´dorsalis

The monoamine levels in the locus coeruleus (LC) were determined by HPLC following specific lesions of the ventral mesencephalic tegmental-A10 regions (VMT-A10) and raphé dorsalis (RD). Only lesions in the VMT-A10 area decreased the dopamine (DA) content, which strongly suggests that the projection from this region to the LC is of dopaminergic nature. Lesions of the RD increased DA metabolism in the LC and provoked significant decreases in the serotonin (5-HT) levels.

Effect of In Vivo Modulation of Membrane Docosahexaenoic Acid Levels on the Dopamine-Dependent Adenylate Cyclase Activity in the Rat Retina

Abstract: We have studied the effect of a dietary deprivation of n‐3 fatty acids on the activity of the dopamine (DA)‐de‐pendent adenylate cyclase in the rat retina. Experiments were conducted in 6‐month‐old rats raised on semipurified diets containing either safflower oil (n‐3 deficient diet) or soybean oil (control diet). The levels of docosahexaenoic acid [22:6 (n‐3)] in retinal phospholipids were significantly decreased in n‐3 deficient rats (35–42% of control levels). This was compensated by a rise in 22:5 (n‐6), the total content of poly‐unsaturated fatty acids (PUFA) remaining approximately constant. Adenylate cyclase activity was measured in retinal membrane preparations from dark‐adapted or light‐exposed rats. The enzyme activity was stimulated by DA and SKF 38393 in a light‐dependent fashion. The activation was lower in rats exposed to light than in dark‐adapted animals, suggesting a down‐regulation of the DI DA receptors by light. The activation by guanine nucleotides and forskolin was also decreased in light‐exposed rats. There was no significant effect of the dietary regimen on the various adenylate cyclase activities and their response to light. Furthermore, the guanine nucleotide‐ and DA‐dependent adenylate cyclase activities of retinal membranes were found to be relatively resistant to changes in membrane fluidity induced in vitro by benzyl alcohol. The results indicate that in the absence of changes in total PUFA content, a decreased ratio of n‐3 to n‐6 fatty acids in membrane phospholipids does not significantly affect the properties of adenylate cyclase in the rat retina.

Brain catecholamines and sleep states in offspring of caffeine-treated rats

Caffeine was administered in the diet to rats throughout gestation. In the 2 consecutive untreated generations, an increase of parodoxical sleep was observed at maturity. In the 1st generation, the dopamine level was markedly reduced in the locus coeruleus, whereas that of noradrenaline remained constant. The effect was less pronounced in the 2nd generation.

Pharmacological investigation on the role of dopamine in the rat locus coeruleus.

The role of dopamine (DA) in the rat locus coeruleus (LC) was investigated by determining the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), DA and noradrenaline (NA) in the LC after pharmacological treatments by pargyline, haloperidol, 6-hydroxydopamine (6-OHDA) and desmethylimipramine (DMI). The DA, DOPAC and NA contents of the LC were determined by high pressure liquid chromatography. Fifteen days after 6-OHDA, the DOPAC and NA levels were reduced by 60%, but they remained constant after 6-OHDA + DMI. Pargyline provoked highly significant increases in DA and NA but reduced DOPAC to non-measurable amounts. haloperidol caused a 54% decrease in the DOPAC levels. Pargyline and haloperidol administered to rats having received 6-OHDA + DMI 15 days before, caused similar effects on DA, DOPAC and NA levels as those in non-treated rats. It is suggested that DOPAC is mainly located in noradrenergic neurons, thus eliminating the possibility of a significant DA cell body population in the rat LC.

Development of hypertension in spontaneously hypertensive rats fed l -tyrosine-supplemented diets

SummaryThe blood pressure of spontaneously hypertensive rats (SHR) was measured by tail-plethysmography. Feeding SHR a diet supplemented with 0.6 g%l-tyrosine, for 15 weeks after weaning, resulted in a slower increase of blood pressure than in rats fed the control diet (no tyrosine added). The blood pressure stabilized, after about 8 weeks, at values lower by about 10 mm Hg than in the control SHR group. Diets with a higher content of freel-tyrosine (1.2 or 2.4 g%) produced no greater hypotensive effects, despite the fact that the plasma level of the amino acid, at the time of blood pressure measurements, was related to the tyrosine content of the diet. In addition, providing 2.4 g% freel-tyrosine to the diet of SHR with established hypertension, produced within a few days a decrease of blood pressure similar to the one recorded in rats fed the tyrosine-supplemented diet during the whole period of development of hypertension. A maximal effect ofl-tyrosine, in decreasing the blood pressure of SHR, is thus obtained at relatively low concentrations of the amino acid in the diet, and after a short period of consumption. However, this effect is rather small, and rapidly reversed upon removing freel-tyrosine from the diet.ZusammenfassungDer Blutdruck von spontanen Hochdruck-Ratten (SHR) wurde durch Plethysmographie am Schwanz gemessen. Die Fütterung einer mit 0,6 g%l-Tyrosin supplementierten Futterration an SHR für 15 Wochen nach dem Absetzen ergab eine langsamere Zunahme des Blutdruckes im Vergleich zu Kontrollratten (ohne zugesetztesl-Tyrosin). Der Blutdruck stabilisierte sich nach ungefähr 8 Wochen mit Meßwerten, welche etwa 10 mm Hg tiefer lagen als in den Kontrollen. Futterrationen mit höheren Gehalten anl-Tyrosin (+1,2 und +2,4 g%) erzeugten keine weitere Blutdruckerniedrigung, obwohl das Plasmaniveau dieser Aminosäure zur Zeit der Blutdruckmessung dem Tyrosingehalt des Futters entsprach. In SHR mit ausgebildetem Hochdruck erniedrigte eine Futterration mit 2,4 g% freieml-Tyrosin innerhalb weniger Tage den Blutdruck auf ein ähnliches Niveau wie in Ratten, welchen während der ganzen Versuchsperiode Tyrosin verabreicht wurde. Ein maximaler Effekt ist so schon mit relativ niedrigen Konzentrationen vonl-Tyrosin nach kurzer Zeit der Verabreichung im Futter erreicht. Dieser Effekt ist jedoch ziemlich klein und verschwindet nach Einstellung derl-Tyrosin-Verabreichung rasch.