Histochemical fluorescence after application of neurochemicals to caudate nucleus and septal area in vivo

The movement of carbachol, norepinephrine, and dopamine from cannula sites in caudate nucleus and septal area of freely moving rats was traced by means of biogenic amine fluorescence. Fluorescent patterns seen after application of carbachol and norepinephrine to brain tissue did not appear to differ from controls. Three types of movement from the cannula site after administration of dopamine were observed. There was a spherical distribution approximately 2 millimeters in diameter. Fluorescence also followed axonal pathways in the orthodromic direction, suggesting that dopamine may have been transported by " axonal streaming " or by some other unknown mechanism in periaxonal spaces. Because fluorescence was present in both the ependymal lining and the choroid plexus, it was inferred that the cerebral ventricles were also involved in the movement of chemical. Any attempt to ascribe anatomical localization to behavioral effects resulting from chemical stimulation of the brain should take into account the widespread movement of chemicals after their local application to brain tissue.     

Dopamine synthesis: stimulation by a hypothalamic factor

The effect of treatment with the factor that inhibits the release of melanocyte stimulating hormone (MSH) identified as 1-prolyl-1-leucylglycinamide (MIF) on brain catecholamine synthesis was examined in normal and hypophysectomized rats. The tripeptide induced a dose-related increase in striatal dopamine synthesis in slices obtained from treated normal animals but not in hypophysectomized animals. Hypothalamic norepinephrine synthesis was unaltered by MIF treatment in normal as well as in hypophysectomized rats. In addition, dopamine and norepinephrine syntheses were depressed in untreated hypophysectomized animals, as compared to normal controls. These results constitute the first direct demonstration of a central neurochemical effect of a hypothalamic factor.     

Adenosine 3',5'-monophosphate content in rat caudate nucleus: demonstration of dopaminergic and adrenergic receptors

Dopamine, apomorphine, isoproterenol, and norepinephrine each increased the concentration of adenosine 3',5'-monophosphate in slice of rat caudate nucleus. The concentrations of dopamine, apomorphine isoproterenol, and norepinephrine causing half-maximal increases were 60, 150, 0.03 and 30 micromoles per liter, respectively. The effect of dopamine was blocked by fluphenazine, a dopamine receptor antagonist, but not by propranolol, a beta-andrenergic receptor antagonist. Conversely, the effect of isoproterenol was blocked by propranolol but not by fluphenazine. The results suggest that in rat caudate nucleus there are two distinct catecholamine receptors capable of causing increased concentrations of adenosine 3',5'-monophosphate, one having the characteristic of dopamine receptor, and the other having the characteristics of beta-adrenergic receptor.     

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.     

Amphetamine: differentiation by d and l isomers of behavior involving brain norepinephrine or dopamine

d-Amphetamine is markedly more potent an inhibitor of catecholamine uptake by norepinephrine neurons in the brain than is 1-amphetamine, whereas the two isomers are equally active in inhibiting catecholamine uptake by the dopamine neurons of the corpus striatum. In behavioral studies, d-amphetamine is ten times as potent as 1-amphetamine in enhancing locomotor activity, while it is only twice as potent in eliciting a compulsive gnawing syndrome. This suggests that the locomotor stimulation induced by amphetamine involves central norepinephrine, while dopamine neurons play an important role in the induced compulsive gnawing behavior. Assessment of differential actions of d- and 1-amphetamine may be an efficient method to differentiate behaviors involving norepinephrine or dopamine in the brain.     

Proportional release of norepinephrine and dopamine- -hydroxylase from sympathetic nerves

Dopamine-beta-hydroxylase(DBH), the enzyme that catalyzes the conversion of dopamine to norepinephrine, is localized in the vesicles containing catecholamine in sympathetic nerves. This enzyme is released with norepinephrine when the nerves to the guinea pig vas deferens are stimulated in vitro, and the amount of enzyme discharged increases as the length of stimulation periods increases. The amount of DBH released is proportional to the amount of norepinephrine released, and the ratio of norepinephrine to DBH discharged into the incubation medium is similar to that in the soluble portion of the contents of the synaptic vesicles from the vas deferens. These data are compatible with the release of the neurotransmitter norepinephrine and DBH from symnpathetic nerves by a process of exocytosis.     

NOREPINEPHRINE AND 3,4DIHYDROXYPHENETHYLAMINE TURNOVER IN GUINEA PIG BRAIN IN VIVO

By administering C(14)-la-beled tyrosine or H(3)-labeled 3,4-dihy-droxyphenylalanine to guinea pigs it has been possible to achieve sufficient labeling of the norepinephrine and dopamine in the brain to permit measurement of their turnover rates. The half-life of brain dopamine was about 2.5 hours. The half-life of norepinephrine was about 4 hours, suggesting a rate of synthesis of at least 0.03 to 0.04, microg/g per hr or 2.4 microg/day for the whole guinea pig brain.     

Facilitation of brain self-stimulation by central administration of norepinephrine

Rats with electrodes implanted in the medial forebrain bundle stimulated their own brains at sharply reduced rates after systemic administration of disulfiram or intraventricular administration of diethyldithiocarbamate. Both drugs inhibit dopamine-beta-hydroxylase, the enzyme responsible for the final step in the biosynthesis of norepinephrine. The suppressed behavior was reinstated by intraventricular injections of 1-norepinephrine, but not by injection of its biologically inactive isomer, d-norepinephrine. Intraventricular administration of dopamine and serotonin did not restore self-stimulation. The rewarding effect of medial forebrain bundle stimulation may depend on the availability of norepinephrine as a transmitter, but not on dopamine or serotonin.     

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.     

Octopamine: presence in single neurons of Aplysia suggests neurotransmitter function

Octopamine has been identified and measured in individual neurons from Aplysia californica. Neither dopamine nor norepinephrine was detected in these cells. Thus, in Aplysia there may be separate populations of catecholaminergic and monophenolaminergic cells. Octopamine may have functions of its own in the central nervous system of mollusks.     

Neurochemical correlate of a spatial preference in rats

Spatial (left or right) preferences were determined for rats given foot shock in a T-maze. The animals were killed, and left and right striata were assayed separately for dopamine and left and right teldiencephalic regions were assayed for norepinephrine. Dopamine content was significantly higher (by 12 percent) in the striata contralateral to rats' side preferences than in the ipsilateral striata; there was no such difference for teldiencephalic norepinephrine. The small asymmetry in striatal dopamine content is not due to any learning- or stress-related change induced by the testing procedure but is probably inherent in normal rats. Some spatial behavior appears to be the manifestation of a normal and specific difference in the activity of left and right nigrostriatal systems.     

L-dopa: effect on concentrations of dopamine, norepinephrine, and serotonin in brains of mice

Large doses of L-dopa given to mice produced marked increases in brain dopamine, no change in norepinephrine, and a remarkable decrease in brain serotonin. This reduction apparently results from a release or displacement, or both, of serotonin from its storage sites.     

Cloning and expression of a cocaine-sensitive rat dopamine transporter

The action of dopamine and other monoamine neurotransmitters at synapses is terminated predominantly by high-affinity reuptake into presynaptic terminals by specific sodium-dependent neurotransmitter transport proteins. A complementary DNA encoding a rat dopamine transporter has been isolated that exhibits high sequence similarity with the previously cloned norepinephrine and gamma-aminobutyric acid transporters. Transient expression of the complementary DNA in HeLa cells confirms the cocaine sensitivity of this transporter.     

Hyperactivity and brain catecholamines in lead-exposed developing rats

Newborn rats that suckled mothers eating a diet containing 4 percent lead carbonate display hyperactivity, aggressiveness, and excessive stereotyped behavior starting at 4 weeks of age. There is an eightfold increase in the concentration of lead in brain, no change in norepinephrine, but a 20 percent decrease in dopamine relative to coetaneous controls. This suggests a relationship between central nervous system dysfunction due to lead and dopamine metabolism in brain.     

Deficits in feeding behavior after intraventricular injection of 6-hydroxydopamine in rats

Intraventricular injections of 6-hydroxydopamine produced 95 percent depletion of telencephalic norepinephrine and 62 percent depletion of striatal dopamine in rats. Treated rats maintained body weight at subnormal levels and failed to increase food intake in response to a short-term decrease in glucose utilization. After treatment with the monoamine oxidase inhibitor pargyline, 6-hydroxydopamine produced no further norepinephrine depletion but increased the dopamnine depletion to 95 percent and produced complete aphagia. These effects are comparable to events that follow bilateral electrolytic lesions of the lateral hypothalanmus.     

Tricyclic antidepressants: evidence for an intraneuronal site of action

Desipramine, a tricyclic antidepressant drug, almost completely prevents the accumulation of tritiated norepinephrine by sympathetic neurons of the rat heart after the injection of a tracer dose of the labeled amine. However, desipramine does not alter the accumulation of norepinephrine after the injection of a large dose of the neurohormone. Despite the failure of desipramine to block the neuronal uptake of norepinephrine, it still prevents exogenous norepinephrine from displacing the endogenous neurohormone (previously labeled with H(3)-norepinephrine) from intraneuronal storage sites.     

Dopamine-beta-hydroxylase: evidence for increased activity in sympathetic neurons during psychotic states

Tritiated dopamine was infused into psychiatric patients during acute psychotic episodes and in remission. An index of the activity of dopamine-beta-hydroxylase of salivary gland sympathetic neurons was determined by measuring the distribution of tritiated metabolites in salivary fluid. Increased synthesis of norepinephrine occurred in acute schizophrenia and in the manic state of manic-depressive psychosis but not in the depressed phase.     

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.     

Tissue levels of norepinephrine and epinephrine in hemorrhagic shock

Severe depletion of endogenous norepinephrine was observed in the brain, heart, liver, and spleen of albino rabbits in which hemorrhagic shock had been induced. On the other hand, the epinephrine content of these tissues was significantly elevated above the levels in tissues of control animals. The norepinephrine and epinephrine levels of skeletal muscle in shocked animals remained unaffected.     

Inhibition of biogenic amine uptake by hydrogen peroxide: a mechanism for toxic effects of 6-hydroxydopamine

Hydrogen peroxide, dialuric acid, or 6-hydroxydopamine inhibited the uptake of dopamine, norepinephrine, and serotonin into rat brain synaptosomal preparations. The addition of catalase protected all systems, but catalase was only partially protective for 6-hydroxydopamine acting upon catecholamine uptake. The data show that 6-hydroxydopamine generates hydrogen peroxide and that hydrogen peroxide can damage the biogenic amine uptake systems. Part of the damage caused by the 6-hydroxydopamine that accumulates in the catecholamine nerve terminals in vivo may be attributed to the hydrogen peroxide.