Dopamine: release from the brain in vivo by amantadine

After dopamine stores in the caudate nucleus of cats were labeled with [(3)H]dopamine, the ventricular system was perfused with artificial cerebrospinal fluid. The addition of amantadine to the perfusing fluid caused a doserelated increase in the concentrations of [(3)H]dopamine appearing in the perfusion effluent. Subthreshold concentrations of amantadine also enhanced the efflux of [(3)H]dopamine induced by electrical stimulation of the caudate nucleus.     

Tritiated norepinephrine: release from brain slices by electrical stimulation

Slices of rat brain and heart that had concentrated H(3)-norepinephrine were superfused and electrically stimulated. Stimulation induced a marked release of H(3)-norepinephrine with a threshold and a maximum repsonse. Release also occurred with increased concentrations of potassium, presumably due to neuronal depolarization. Inhibition of electrically induced release occurred with low calcium and with chlorpromazine and pentobarbital.     

Evoked release of norepinephrine and serotonin from brain slices: inhibitoon by lithium

Slices of mammalian brain accumulate H(3)-norepinephrine and H(3)-serotonin when incubated in a physiologic medium containing these tritiated monoamines. When these tissues are subjected to mild electrical stimulation of short duration, which is associated with depolarization of nerve membranes, a striking increase in the rate of efflux of the exogenous labeled monoamines occurs. Stimulation-induced release of both labeled monoamines is diminished by the presence of lithium ions in the perfusing medium; related monovalent cations had no such effect. Evoked release from slices of brain from animals treated intraperitoneally with lithium chloride for 3 days was also reduced.     

Norepinephrine pools in rat brain: differences in turnover rates and pathways of metabolism

The rate of disappearance of intracisternally administered [(3)H]norepinephrine from rat brain gradually declines as a multiphasic exponential function of time. Conversion to [(3)H]normetanephrine accounts for a larger fraction of the [(3)H]norepinephrine released in the brain shortly after its intracisternal injection than that released at later times. Pools of norepinephrine in the brain thus appear to differ in their turnover rates and pathways of metabolism. The pool of norepinephrine with a rapid rate of turnover and an appreciable conversion to normetanephrine, identified by the techniques reported here, may correspond to a pool of newly synthesized norepinephrine in the brain.     

Norepinephrine turnover and metabolism in rat brain after long-term administration of imipramine

The rate of disappearance of intracisternally administered tritiated norepinephrine from rat brain is decreased after a single dose of the tricyclic antidepressant imipramine. During long-term administration of imipramine, however, the rate of disappearance of tritiated norepinephrine from brain gradually increases, and there is a concurrent decrease in the content of endogenous norepinephrine in brain. These findings may help to explain why antidepressant effects are observed clinically only after long-termn treatment with imipramine.     

Norepinephrine and dopamine: assay by mass fragmentography in the picomole range

Gas chromatography-mass spectrometry makes possible the simultaneous measurement of norepinephrine and dopamine in concentrations of 0.1-milligram tissue samples. Specificity of the assay is confirmed both by the retention time of the compound and by the mass to charge ratio of the fragments recorded. The sensitivity is of the order of 0.5 picomole, and linearity of the response is maintained up to at least 200 picomoles.     

Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow

Bone marrow stem cells give rise to a variety of hematopoietic lineages and repopulate the blood throughout adult life. We show that, in a strain of mice incapable of developing cells of the myeloid and lymphoid lineages, transplanted adult bone marrow cells migrated into the brain and differentiated into cells that expressed neuron-specific antigens. These findings raise the possibility that bone marrow-derived cells may provide an alternative source of neurons in patients with neurodegenerative diseases or central nervous system injury.     

Phenylketonuria: phenylalanine inhibits brain pyruvate kinase in vivo

The hypothesis that brain damage in phenylketonuria is related to inhibition of pyruvate kinase by phenylalanine was examined in rat brain in vivo. One hour after a single injection of phenylalanine into the rat, the brains were removed and completely frozen in less than a second. The concentration of phenylalanine in the brain was comparable to that found in phenylketonuric patients. Changes in brain glycolytic intermediates were consistent with inhibition of pyruvate kinase in vivo. The inhibition of pyruvate kinase was apparently compensated for by an increase in phosphoenolpyruvate; no decrease in adenosine triphosphate or creatine phosphate was found.     

Norepinephrine synthesis from tyrosine-C-14 in isolated perfused guinea pig heart

The isolated, perfused guinea pig heart contains all the catalysts required to form norepinephrine from the dietary precursor, tyrosine. The conversion of tyrosine-C(14) to norepinephrine in the perfused heart occurred at a rate comparable to that estimated for this conversion in vivo. To account for the maintenance of norepinephrine stores in the normal heart, it is not necessary to postulate that the hormone is extracted from the blood.     

Psychotomimetic N-methylated tryptamines: formation in brain in vivo and in vitro

The use of a sensitive enzymatic assay demonstrates that tryptamine occurs normally in rat brain. Intracisternal administration of [(14)C]tryptamine results in the formation of N-methyl-and dimethyltryptamine(a psychotomimetic compound)in the rat brain. An enzyme that converts tryptamine and N-methyl-tryptamine to N-methyl-and dimethyltryptamine was found to be present in rat and human brain. The N-methylation of tryptamine was inhibited by normally occurring compounds present in rat brain.     

Nicotinic cholinergic receptor binding sites in the brain: regulation in vivo

Tritiated acetylcholine was used to measure binding sites with characteristics of nicotinic cholinergic receptors in rat brain. Regulation of the binding sites in vivo was examined by administering two drugs that stimulate nicotinic receptors directly or indirectly. After 10 days of exposure to the cholinesterase inhibitor diisopropyl fluorophosphate, binding of tritiated acetylcholine in the cerebral cortex was decreased. However, after repeated administration of nicotine for 10 days, binding of tritiated acetylcholine in the cortex was increased. Saturation analysis of tritiated acetylcholine binding in the cortices of rats treated with diisopropyl fluorophosphate or nicotine indicated that the number of binding sites decreased and increased, respectively, while the affinity of the sites was unaltered.     

Acetylcholine: release from neural tissue and identification by pyrolysis--gas chromatography

Gas chromatographic analysis showed acetylcholine to be the only choline ester released from innervated longitudinal muscle of the guinea pigileum by electrical stimulation. The amount of acetylcholine measured by gas chromatography agreed almost exactly with that measured by bioassay. Denervated longitudinal muscle produced no acetylcholine, and treatment of the muscle with tetrodotoxin markedly reduced acetylcholine output. The method permits the recovery and quantitation of amounts of acetylcholine as low as 5 nanograms in 5 milliliters of tissue perfusates.     

Norepinephrine biosynthesis inhibition: effects on memory in mice

Diethyldithiocarbamate, a dopamine beta hydroxylase inhibitor, decreases biosynthesis of norepinephrine in the brain. The effects of this inhibitor coincide with alterations in memory as demonstrated in single-trial passive avoidance in C57BL/6J mice.     

Thiamine release from nerve membranes by tetrodotoxin

Tetrodotoxin (3 x 10(-8) molar) promoted the release of thiamine from perfused rat and frog nerve preparations in a manner similar to other neuroactive drugs. When the rats were injected with thiamine labeled with sulfur-35, analyses of brain, spinal cord, and sciatic nerve homogenates revealed labeled thiamine in membrane, synaptosomes, and mitochondrial subfractions. However, on incubation of these fractions with tetrodotoxin, thiamine was released only from the membrane fragments.     

Magnesium pemoline: failure to affect in vivo synthesis of brain RNA

The effect of magnesium pemoline on the synthesis of brain RNA in vivo was studied. No significant effect either on the concentration of RNA or on the uptake of H(3)-uridine into RNA was detected.     

Norepinephrine in chronic paranoid schizophrenia: above-normal levels in limbic forebrain

In postmortem examination of brains of four patients with chronic paranoid schizophrenia, above-normal norepinephrine levels were measured in the ventral septum, the bed nucleus of the stria terminalis, the nucleus accumbens, and the mammillary bodies. No changes were detected in other limbic forebrain regions, including the hypothalamus and the medial olfactory (preoptic) area. The results point to the possibility of a malfunction of limbic noradrenergic mechanisms in schizophrenia, especially the paranoid variety.     

Norepinephrine: reversal of anorexia in rats with lateral hypothalamic damage

Injection of norepinephrine in the lateral ventricles of rats recovering from lateral hypothalamic anorexia caused immediate feeding and, frequently, overeating. Intraventricular administration of the alpha-noradrenergic blocker, phentolamine, suppressed feeding in both normal rats and rats that had recovered from lateral hypothalamic lesions. Feeding is reinforced by ascending medial forebrain bundle fibers that form alpha-noradrenergic synapses in the hypothalamus and forebrain. Damage to these fibers suppresses feeding by reducing noradrenergic transmission and, hence, the rewarding value of food. Recovery of feeding after hypothalamic lesions coincides with the recovery of noradrenergic reward function.     

Norepinephrine methylation in fetal rat adrenals

The activity of phenylethanolamine-N-methyl transferase, the enzyme that methylates norepinephrine to form epinephrine, increases rapidly in the fetal rat adrenal during the day preceding epinephrine accumulation. The developmental increase in enzyme activity and the accumulation of epinephrine are prevented by fetal hypophysectomy (decapitation). Administration of adrenocorticotrophic hormone or cortisol acetate largely reverses the effect of fetal decapitation.     

Progesterone administration in vivo stimulates release of luteinizing hormone-releasing hormone in vitro

The release of luteinizing hormone-releasing hormone (LHRH) from tissue from the mediobasal hypothalamic-anterior hypothalamic-preoptic area of prepuberal female rats was measured in a perfusion system. Measurements were also made of the concentrations of LHRH in these tissue fragments and of luteinizing hormone in serum obtained when the rats were killed. Four groups of immature rats were studied: intact, ovariectomized, ovariectomized and implanted with estradiol-containing capsules, and ovariectomized rats primed with estradiol and injected with progesterone. The release of LHRH from the tissue of ovariectomized animals was significantly less than that of intact females and was not modified when the ovariectomized rats received estradiol. However, there was a four- to fivefold increase in LHRH release from tissue of ovariectomized rats primed with estradiol when they were killed 6 hours after they received an injection of progesterone. The concentrations of LHRH in tissue and of luteinizing hormone in serum varied among groups and with the time of day that the animals were killed. The interactions among luteinizing hormone, gonadal steroids, and the photoperiod seem to set the appropriate conditions for neural processes triggering a complete and normal release of luteinizing hormone.