Richard J. Wurtman

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: 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.

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.

A simple and rapid method for injecting H3-norepinephrine into the lateral ventricle of the rat brain

Abstract A simple and direct method of labelling brain norepinephrine stores, via injection into the lateral ventricle is described. H 3 -norepinephrine introduced by this procedure was found to be distributed evenly in both sides of the brain. The accumulation of H 3 -norepinephrine in various brain regions parallels that of endogenous levels of norepinephrine and the amine is selectively localized in the “nerve endings”. The disappearance of H 3 -norepinephrine administered by the direct injection technique and its modification by drugs are similar to that of material introduced by stereotaxic procedures.

Partial lesions of the dopaminergic nigrostriatal system in rat brain: biochemical characterization

Various doses of 6-hydroxydopamine injected into the rat substantia nigra produced partial, dose-dependent lesions of the dopaminergic nigrostriatal tract. The resulting reduction in striatal dopamine concentrations and tyrosine hydroxylase activities tended to be proportional, allowing these measurements to serve as indices for lesion severity in any particular animal. Lesions destroying two-thirds or more of the nigrostriatal neurons accelerated dopamines synthesis in, and release from, surviving neurons, as indicated by increased striatal levels of the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid. Formation of these metabolites was also enhanced in dendrites of dopaminergic neurons in the substantia nigra. Supersensitivity of striatal postsynaptic receptors, as judged by induction of rotational behavior after apomorphine or L-DOPA administration, occurred when 90% or more of the nigrostriatal neurons had been destroyed. In contrast, rotational behavior could be induced by amphetamine in animals with only 50% of these neurons destroyed.

Melatonin Synthesis in thePineal Gland: Control by Light

In rats placed in continuous darkness for 6 days, there is a striking increase in the activity of melatonin-synthesizing-enzyme (hydroxyindole-0-methyl transferase) in the pineal gland, but no change in the activity of monoamine oxidase. Since melatonin appears to have a hormonal role in mammals, and its synthesis is confined to the pineal gland, the inhibition of hydroxyindole-O-methyl transferase by light may constitute a mechanism of neuroendocrine regulation.

The effects of low doses of caffeine on human performance and mood

Caffeine is thought to have stimulant-like behavioral effects on mood and performance. However few behavioral studies have examined this substances acute effects when administered in a range of doses that include the low doses typically found in foods and over-the-counter drugs. We therefore gave single doses of caffeine (32, 64, 128 and 256 mg) to 20 healthy male subjects and assessed various aspects of performance and self-reported mood states, as well as plasma caffeine concentration. As little as 32 mg (which elevated plasma caffeine concentration to less than 1 μg/ml), typical of the dose found in a single serving of a cola beverage, and less than that found in a single cup of coffee or a single dose of over-the-counter drugs, significantly improved auditory vigilance and visual reaction time. All other caffeine doses administered also significantly improved performance on these tests. No adverse behavioral effects, such as increased anxiety or impaired motor performance, were noted even at the highest dose administered.

Brain catechol synthesis - Control by brain 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.

Brain acetylcholine: Increase after systematic choline administration

Abstract Administration of choline chloride i.p. to rats causes a dose-dependent increase in the brain concentration of the neurotransmitter, acetylcholine (ACh). This increase is maximal (22% after a 60-mg/kg dose) 40 minutes after injection. These observations suggest that precursor availability may influence brain ACh synthesis, just as brain tryptophan and tyrosine levels have previously been shown to control the synthesis of brain serotonin and catecholamines.

Adrenaline Synthesis: Control by the Pituitary Gland and Adrenal Glucocorticoids

The activity of phenylethanolamine-N-methyl transferase, an enzyme that synthesizes adrenaline from noradrenaline in the adrenal medulla, is markedly depressed following hypophysectomy. Enzyme activity is restored to normal after administration of ACTH or the potent glucocorticoid, dexamethasone. Thus the biosynthesis of adrenaline in the adrenal medulla appears to be regulated by the pituitary-adrenocortical system.