Brain acetylcholine: control by dietary choline.

Acetylcholine concentrations in whole rat brain or in various brain regions and free choline concentrations in blood serum and brain vary with dietary choline consumption. The increases in brain acetylcholine after treatment with physositigmine (an inhibitor of actylcholinesterase) or after consumption of a diet high in choline are additive, suggesting that choline acts by increasing acetylcholine synthesis.

Choline administration: activation of tyrosine hydroxylase in dopaminergic neurons of rat brain.

The administration of choline in doses previously shown to elevate brain acetylcholine concentrations also increases the activity of tyrosine hydroxylase in rat caudate nuclei. This response can be blocked by atropine, a muscarinic antagonist. These findings indicate that choline-induced increases in acetylcholine concentrations may be associated with parallel changes in the amount of the neurotransmitter released into synapses.

Short-term variations in diet composition change the pattern of spontaneous motor activity in rats.

The nocturnal activity patterns of rats changed significantly within 3 days after they were given unrestricted access to isocaloric diets in which the ratio of carbohydrate to protein was systematically varied. As the ratio increased, the rats were more continuously active. The subjects showed similar responses to variations in this ratio whether the diet contained 15 or 45 percent fat. No correlation was found between the number of calories an animal ate and its activity pattern.

Sucrose consumption early in life fails to modify the appetite of adult rats for sweet foods.

Male rats consumed a diet containing 0, 12, or 48 percent sucrose on days 16 to 30 of life. Thereafter, they had simultaneous access to all three diets until day 63. No relationship was detected between sucrose consumption early in life and subsequent preference for sucrose. The onset of puberty was associated with a decreased appetite for sucrose among animals of both sexes.

Choline and cholinergic neurons.

Mammalian neurons can synthesize choline by methylating phosphatidylethanolamine and hydrolyzing the resulting phosphatidylcholine. This process is stimulated by catecholamines. The phosphatidylethanolamine is synthesized in part from phosphatidylserine; hence the amino acids methionine (acting after conversion to S-adenosylmethionine) and serine can be the ultimate precursors of choline. Brain choline concentrations are generally higher than plasma concentrations, but depend on plasma concentrations because of the kinetic characteristics of the blood-brain-barrier transport system. When cholinergic neurons are activated, acetylcholine release can be enhanced by treatments that increase plasma choline (for example, consumption of certain foods).

Fenfluramine and fluoxetine spare protein consumption while suppressing caloric intake by rats.

The effects of fenfluramine and other sanorectic drugs on the consumption of both protein and total calories by rats given simultaneous access to two isocaloric diets containing 5 or 45 percent casein were examined. Anorectic doses of fenfluramine failed to decrease protein intake but increased the proportion of total dietary calories represented by protein. In contrast, anorectic doses of d-amphetamine decreased protein and calorie consumption proportionately. Subanorectic doses of fenfluramine also increased the proportion of caloric intake represented by protein among animals given prior treatment with the serotonin precursor tryptophan. Fluoxetine, a drug that blocks reuptake of serotonin, similarly spared protein consumption while reducing caloric intake. These observations indicate that two distinct brain mechanisms, sensitive to different drugs, underlie the elective consumption of protein and calories.

Lecithin consumption increases acetylcholine concentrations in rat brain and adrenal gland.

Consumption of a single meal containing lecithin, the major source of choline occurring naturally in the diet, increased the concentrations of choline and acetylcholine in rat brain and adrenal gland. Hence, the concentration of acetylcholine in the tissues may normally be under direct, short-term nutritional control.

Brain serotonin content: physiological regulation by plasma neutral amino acids.

When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain.

Brain serotonin content: increase following ingestion of carbohydrate diet.

In the rat, the injection of insulin or the consumption of carbohydrate causes sequential increases in the concentrations of tryptophan in the plasma and the brain and of serotonin in the brain. Serotonin-containing neurons may thus participate in systems whereby the rat brain integrates information about the metabolic state in its relation to control of homeostatis and behavior.

Cyclic adenosine monophosphate: stimulation of melatonin and serotonin synthesis in cultured rat pineals.

Dibutyryl cyclic adenosine monophosphate, like norepinephrine, stimulates the synthesis of labeled melatonin and serotonin from tryptophan labeled with carbon-14 by rat pineals in organ culture. Unlike norepinephrine, dibutyryl cyclic adenosine monophosphate does not enhance the accumulation of labeled tryptophan or protein within the pineal. These findings are compatible with the hypothesis that cyclic adenosine monophosphate mediates some, but not all, of the effects of norepinephrine.

Daily rhythm in tyrosine concentration in human plasma: persistence on low-protein diets.

The concentration of tyrosine in the plasma of normal males varies diurnally. It is lowest (9.5 +/- 0.35 micrograms per milliliter) between 0130 and 0230 hours and rises to a peak of 16.2 +/- 0.82 micrograms per milliliter by 1030 hours. This rhythm persists when subjects are maintained for 2 weeks on a diet that is very low in protein.

Norepinephrine: turnover in rat brains after gonadectomy.

The rate at which (3)H-norepinephrine disappears from rat braint increases after gonadectomy; the effect is observed 6 days after the operation and 24 hours after introduiction of the labeled mnaterial; it is not reprodluced by hypophysectomy. The content of endogenouis brain norepinephrinie does not decline after removal of the ovaries or testes; thus synlthesis of the catecholamine is probably increased by these procedures.

Pituitary serotonin content: effects of melatonin or deprivation of water.

Relatively high concentrations of serotonin are found in the three regions of the rat pituitary gland. Administration of melatonin causes a selective increase in the serotonin concentration of the pars intermedia; deprivation of water for 5 days causes a selective decrease in the serotonin concentrations of the neural lobe and pars distalis.

Brain serotonin content: physiological dependence on plasma tryptophan levels.

Brain serotonin cocentrations at 1 p.m. were significantly elevated 1 hour after rats received a dose of L-tryptophan (12.5 milligrams per kilogram. intraperitoneally) smaller than one-twentieth of the normal daily dietary intake. Plasma and brain tryptophan levels were elevated 10 to 60 minutes after the injection, but they never exceeded the concentrationis that occur nocturnally in untreated aninmals as result of their normal 24-hour rhythms. These data suggest that physiological changes in plasma tryptophan concentration influenice brain serotonin levels.

Perinatal undernutrition: accumulation of catecholamines in rat brain.

Brains of rats undernourished from midgestation and killed at weaning contained 25 percent less norepinephrine than brains of adequately fed littermates. Perinatal undernutrition also suppressed the accumulation of brain dopamine. Paradoxically, the activity of tyrosine hydroxylase, the enzyme thought to be rate-limiting in catecholamine biosynthesis, was significantly increased in brains from undernourished animals.

Brain catechol synthesis: control by train tyrosine concentration.

Brain catechol synthesis was estimated by measuring the rate at which brain dopa levels rose following decarboxylase inhibition. Dopa accumulation was accelerated by tyrosine administration, and decreased by treatments that lowered brain tyrosine concentrations (for example, intraperitoneal tryptophan, leucine, or parachlorophenylalanine). A low dose of phenylalanine elevated brain tyrosine without accelerating dopa synthesis. Our findings raise the possibility that nutritional and endocrine factors might influence brain catecholamine synthesis by controlling the availability of tyrosine.

Dihydroxyphenylalanine in rat food containing wheat and oats.

Dopa has been identified in rat food by three different fluorimetric assays and paper chromatography. Incubation of the rat food with proteolytic enzymes dramatically increased the measurable free dopa. Analysis of samples of six individual protein-containing constituents of rat food revealed that both wheat and oats contain dopa.

Tyrosine increases blood pressure in hypotensive rats.

Administration of tyrosine, the amino acid precursor of catecholamines, increased blood pressure 38 to 49 percent in rats made acutely hypotensive by hemorrhage; other large neutral amino acids were ineffective. Tyrosine's effect was abolished by adrenalectomy, suggesting that, in hypotensive animals, it acts by accelerating the peripheral synthesis and release of catecholamines.

Entrainment of the body temperature rhythm in rats: effect of color and intensity of environmental light.

The daily rhythm in body temperature in rats was continuously monitored during exposure to low-intensity environmental illumination of various colors in the visible and near-ultraviolet spectrum. The ability of phase shifts in the lighting schedule to induce concomitant changes in the rhythm was used to determine the spectral sensitivity of the retinal photoreceptor systems mediating rhythm entrainment. Green light (lambda = 530 +/- 45 nanometers) was most potent, and red (lambda = 660 +/- 19 nanometers) and ultraviolet (lambda = 360 +/- 34 nanometers) were least potent in entraining the temperature rhythm.

L-dopa: disaggregation of brain polysomes and elevation of brain tryptophan.

One hour after administration of L-dopa (50 to 300 milligrams per kilogram), there is a marked disaggregation of brain polysomes in immature rats. Adult animals show a similar response, but require larger doses of the amino acid (500 milligrams per kilogram). Single doses of L-dopa significantly elevate amounts of tryptophan in the brain; hence their effect on polysomes does not result from the unavailability of this amino acid.