Showing papers on "Serotonin published in 1969"
TL;DR: It is suggested that in depression the production of tryptophane pyrrolase by the liver is stimulated by raised blood-corticosteroid levels, and the metabolism of tryPTophane is shunted away from serotonin production, and towards kynurenine production.
688 citations
TL;DR: Intracisternal injections of 6-hydroxydopamine produce rapid and long-lasting depletion of brain catecholamines without effects on serotonin concentrations.
Abstract: Intracisternal injections of 6-hydroxydopamine produce rapid and long-lasting depletion of brain catecholamines without effects on serotonin concentrations. Depletion of norepinephrine is greatest in areas containing only nerve terminals and axons and least in areas containing monoamine cell bodies. The norepinephrine loss is accompanied by electron microscopic evidence of nerve terminal degeneration and decreased turnover. Dopamine loss is less marked and is not accompanied by degeneration or alteration of turnover rate.
409 citations
173 citations
TL;DR: 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, and the suppressed behavior was reinstated by intra ventricular injections of 1-norepinephrine, but not by injection of its biologically inactive isomer, d-norpinephrine.
Abstract: 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-β-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.
155 citations
TL;DR: Observations suggest that noradrenaline liberated from sympathetic nerves stimulates the formation of melatonin either by increasing theformation of new melatonin-forming enzyme, by increasing transport of tryptophan into the pineal cell, or by inhibiting the metabolism of serotonin by the alternate deaminating pathway.
Abstract: Previous work has shown that the activity of the melatonin-forming enzyme in the rat pineal gland is elevated in rats kept in continuous darkness as compared to those kept in continuous light. Information about environmental lighting reaches the pineal gland via nerves that liberate noradrenaline. Rat pineal glands in organ culture can form C(14)-melatonin from C(14)-tryptophan as follows: tryptophan --> 5-hydroxytryptophan --> serotonin --> melatonin. Noradrenaline was found to stimulate the synthesis of C(14)-melatonin from C(14)-tryptophan in rat pineals in organ culture. Other compounds related in structure to noradrenaline increase melatonin and serotonin synthesis and inhibit the formation of the deaminated product of serotonin, 5-hydroxyindole acetic acid. Cycloheximide, a compound that inhibits protein synthesis, also prevents the formation of serotonin, melatonin, and 5-hydroxyindole acetic acid from tryptophan in pineal organ culture. These observations suggest that noradrenaline liberated from sympathetic nerves stimulates the formation of melatonin either by increasing the formation of new melatonin-forming enzyme, by increasing transport of tryptophan into the pineal cell, or by inhibiting the metabolism of serotonin by the alternate deaminating pathway.
147 citations
01 Jul 1969
142 citations
TL;DR: The effects of ventromedial tegmental lesions on the biosynthesis and disposition of biogenic amines in the striatum of monkeys were investigated and the concentrations of endogenous dopamine and of the intraventricularly injected [3H]dopamine were distinctly lower on the lesion side than on the intact side.
Abstract: —
The effects of ventromedial tegmental lesions on the biosynthesis and disposition of biogenic amines in the striatum of monkeys were investigated. The concentrations of endogenous dopamine and of the intraventricularly injected [3H]dopamine were distinctly lower in the striatum on the lesion side than on the intact side.
The storage of [3H]dopamine in the caudate nucleus was impaired to a much greater extent than the storage of the newly synthesized [3H]norepinephrine.
The concentrations of endogenous serotonin and of the intraventricularly injected [14C]serotonin were lower in the striatum on the lesion side than on the intact side. However following MAO inhibition, the concentration of [14C]serotonin did not differ significantly on the two sides of the caudate nucleus.
The in vivo biosynthesis of dopamine from tyrosine was significantly reduced in the striatum on the lesion side. Tyrosine hydroxylase and DOPA decarboxylase activities were decreased on the lesion side of the striatum as compared with the intact side. Thus, the ventromedial tegmental lesions affect the storage and the synthesis of dopamine and serotonin in the ipsilateral striatum.
117 citations
TL;DR: Findings suggest that quipazine and serotonin may exert their actions through stimulation of the same type of receptors.
116 citations
TL;DR: Electrical stimulation predominantly affects the liberation of the unchanged amine, rather than of its principal metabolite, 5‐HIAA, in labelled serotonin accumulated by slices of rat brain.
Abstract: —
1. Labelled serotonin ([3H]5-HT) accumulated by slices of rat brain either in vivo or in vitro is released by depolarizing procedures such as electrical stimulation or high external potassium concentrations. Electrical stimulation predominantly affects the liberation of the unchanged amine, rather than of its principal metabolite, 5-HIAA.
2. Release of [3H]5-HT does not appear to be calcium-dependent.
3. Amount of release parallels the density of serotonin-containing nerve terminals in each of several cerebral regions tested. Release from several extracerebral tissues was similar to that obtained from cerebral tissues having relatively little endogenous 5-HT.
4. Electrically induced release of [3H]5-HT is markedly inhibited by desipramine, chlorpromazine, LSD, lithium and ouabain.
101 citations
TL;DR: Elevated calcium concentration prevents lithium-induced inhibition of norepinephrine-3 H release but has no effect on lithium inhibition of evoked release of serotonin- 3 H, and enhanced calcium levels did not reverse ouabain- induced inhibition of release of either monoamine.
100 citations
TL;DR: Depletion of platelet 5HT by the intramuscular administration of Reserpine induces migraine in susceptible individuals, and intravenous 5HT relieves-both spontaneous and reserpine-induced migraine.
Abstract: THE WIDESPREAD use of monoamine oxidase (MAO) inhibitors followed the simultaneous discovery that iproniazid phosphate caused euphoria in tuberculous patients1and inhibited monoamine oxidase.2Since then, they have formed an important group of antidepressant drugs. The clinically important monoamine oxidases are present in the granular fraction of most parenchymatous tissues of vertebrates where they deaminate several aliphatic and aromatic amines, including serotonin (5-hydroxytryptamine [5HT] ), dopamine, tryptamine, tyramine, and, to a lesser extent, epinephrine and norepinephrine. Administration of MAO inhibitors increases the concentration of these amines in many organs, including blood platelets, which contain about 99% of blood 5HT.3 Spontaneous migraine is associated with a fall in plasma 5HT and increased urinary excretion of both 5-hydroxyindole acetic acid (5HIAA)4,5and 5 HT (unpublished observations). Depletion of platelet 5HT by the intramuscular administration of reserpine induces migraine in susceptible individuals, and intravenous 5HT relieves-both spontaneous and reserpine-induced
TL;DR: High blood pressure is not the result of an absence of beta receptor or a hypersensitivity of the vascular smooth muscle, and spontaneously hypertensive rats were less responsive than normal animals to the contractile effects of norepinephrine, serotonin, and potassium chloride.
Abstract: Aortic strips from spontaneously hypertensive rats were less responsive than normal animals to the contractile effects of norepinephrine, serotonin, and potassium chloride but more reactive to the relaxant effects of the stimulant of beta receptors, isoproterenol. Thus, hypertension is not the result of an absence of beta receptor or a hypersensitivity of the vascular smooth muscle.
TL;DR: Neurones were predominantly excited by monoamines in halothane anaesthetised cats and encephale isole preparations, and excitation was still seen when careful controls for current, pH and anion effects were made.
TL;DR: Dibutyryl cyclic adenosine monophosphate stimulates the synthesis of labeled melatonin and serotonin from tryptophan labeled with carbon-14 by rat pineals in organ culture, and does not enhance the accumulation of labeled tryPTophan or protein within the pineal.
Abstract: 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.
TL;DR: The best-known central nervous system effects are mood depression with low cerebral serotonin levels and mood elevation with increased concentrations, and behavior can be experimentally altered in the cat by intraventricular serotonin injection.
Abstract: S EROTONIN, a naturally occurring amine, can be found throughout the mammalian brain although the concentrations in the brain stem, limbic lobe, and hypothalmus are 20 to 40 times greater than those in the cortex, white matter, or cerebellumY 3 The material occupies an intracellular neuronal site, as demonstrated by fluorescent 1%17 and radioisotope 25,46 studies, where it accumulates in synaptic terminals in high concentration. Within the neurons, serotonin is found in morphologically distinct vesicles2 G,46 Apparently the vesicles hold serotonin safe f rom enzymatic destruction by monoamine oxidaseY v Despite extensive investigations, the neurophysiologic function of serotonin remains unknown. The best-known central nervous system effects are mood depression with low cerebral serotonin levels and mood elevation with increased concentrations. 47 Behavior can be experimentally altered in the cat by intraventricular serotonin injection. Sedation, diminished motor activity, lethargy, tremor, and convulsions have all been reported? 9,~9,as The body temperature response to third ventricular injection of serotonin is dose dependent; small doses cause hyperthermia, and larger doses, hypothermiaY
TL;DR: Lesions in the medial forebrain bundle of the rat produced both an increased sensitivity to electric-foot shock and a decrease in the telencephalic content of serotonin, and administration of dl -5-hydroxytryptophan reversed the effects of the lesion on shock sensitivity.
TL;DR: The effect of D-lysergic acid diethylamide is discussed with regard to its action on brain serotonergic neurons and its psychotomimetic effects.
Abstract: Injections of D -lysergic acid diethylamide decrease the turnover rate of 5-hydroxytryptamine of rat brain, as measured from the conversion of 14C-tryptophan into 14C-5-hydroxytryptamine. The 2-bromolysergic acid diethylamide given in doses fivefold greater than those of lysergic acid diethylamide fails to change the rate of 14C-tryptophan conversion into 14C-5-hydroxytryptamine. The effect of D -lysergic acid diethylamide is discussed with regard to its action on brain serotonergic neurons and its psychotomimetic effects.
TL;DR: D-Lysergic acid diethylamide given pareriterally produces a reversible cessation of the spontaneous activity of neuronal units in the midbrain raphe nuclei of the rat.
Abstract: D-Lysergic acid diethylamide (LSD) given pareriterally produces a reversible cessation of the spontaneous activity of neuronal units in the midbrain raphe nuclei of the rat1. Threshold doses of LSD required to produce this effect are extremely small in relation to those typically used in rats (10–20 µg/kg, intravenously). Substances the behavioural effects of which are similar to those of LSD (for example, N,N-dimethyltryptamine and mescaline) also inhibit raphe units, although none is as potent as LSD2. A variety of other types of drugs (for example, atropine, phencyclidine, chlorpromazine) do not affect the activity of raphe units2. The inhibitory effect of LSD is specific for units in the dorsal and median raphe nuclei; in other mid-brain areas (for example, reticular formation), the drug either has no effect or accelerates unit activity1. According to the fluorescence histochemical method the midbrain raphe nuclei are comprised of serotonin-containing neurones3. Axons of the raphe neurones supply the principal serotonin input to the forebrain4. Large doses of LSD induce a prolonged inhibition of the serotonin-containing neurones1; this inhibition may account for the reduced metabolism of brain serotonin observed after injections of LSD5–8.
TL;DR: The purpose of the present report is to demonstrate that the active uptake of 5HT in human blood platelets in vitro requires the presence of sodium as well as chloride, and that choline (Ch+), which is generally considered to be an inert cation, exerts a competitive inhibitory effect on the uptake of5HT.
TL;DR: Levels of radioactive serotonin and deaminated metabolites in brain were increased above control values when lithium chloride was administered after the intracistemal injection of serotonin-14C, and the findings are discussed in relation to studies of the actions of these drugs on the metabolism of endogenous serotonin in brain.
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TL;DR: It is concluded that the regional rhythms of serotonin and norepinephrine concentrations are independently regulated in cat brain.
Abstract: There is a 24-hr (circadian) cycle in the concentration of serotonin in certain regions of the upper brainstem and telencephalon of the cat brain, including parts of the mesencephalon, the medial hypothalamus and most deep nuclei of the telencephalon. In the neocortex, serotonin rhythms are regionally specific. A biphasic or ultradian serotonin rhythm occurs in the substantia nigra-lateral tegmentum region and anterior hypothalamus. A rhythm in serotonin was not found in the cat pineal gland. No sex difference in regional serotonin was found in cat. The regional serotonin rhythms in cat brain are asynchronous and have different forms. Comparison with previous data on regional cycles of norepinephrine indicates that most regions of cat brain have a rhythm of one or the other amine, thereby assuring alteration in the ratios of the concentration of each amine in different brain regions. However, only the substantia nigra-lateral tegmentum region, the anterior hypothalamus and the tuber cinereum share rhythms of both norepinephrine and serotonin, which are generally 180° out of phase. We conclude that the regional rhythms of serotonin and norepinephrine concentrations are independently regulated in cat brain.
TL;DR: The results suggest that the decrease of spontaneous motor activity after p chlorophenylalanine administration is probably not mediated through serotonin or the catecholamines and that another mode ofp-chlorophenylAlanine action must be supposed.
TL;DR: The results indicate that the syntheses of dopamine and serotonin in the striatal and other tissues are dependent on the integrity of separate neuronal systems originating in specific cell groups of the brain stem.
TL;DR: Evidence is presented that indoleacetaldehydes are biologically active and that to some extent their effects mimic the action of serotonin in visual evoked responses7 and sleep induction, two functions known to be affected selectively by serotonin probably because the corresponding pathways are normally modulated by the endogenous amine.
Abstract: SEROTONIN (5HT) and tryptamine are metabolized primarily by monoamine oxidase (MAO)1 with the formation of the corresponding aldehyde derivatives 5-hydroxyindole-3-acetaldehyde (5HIAAld) and indoleacetaldehyde (IAAld). These aldehydes are unstable and reactive and are promptly oxidized to corresponding acids2, are firmly bound to acid-insoluble fractions of brain homogenates2–3 or follow other metabolic routes2,4,5, but they are not significantly reconverted to the corresponding amines3. Little attention has been paid to the possible pharmacological activity of these aldehydes because they are inactive in smooth muscle preparations6. We now wish, however, to present evidence that indoleacetaldehydes are biologically active and that to some extent their effects mimic the action of serotonin in visual evoked responses7 and sleep induction9, two functions known to be affected selectively by serotonin probably because the corresponding pathways are normally modulated by the endogenous amine. Our 5HIAAld was prepared enzymatically from 5HT6 and its concentration determined by the 2,4-dinitrophenylhydrazine method9. Its purity was determined by a combination of electrophoretic separation and subsequent autoradiography3; serotonin was not detectable.
TL;DR: It is suggested that brain 5-HT biosynthesis is not controlled by feedback inhibition, and after pargyline treatment, brain NE and5-HT concentrations increase, but only NE synthesis is inhibited.
TL;DR: Intraperitoneal injections of GABA to rats lowered the level of norepinephrine in brain, heart and spleen but not suprarenals and raised that of serotonin in brain and monoamine oxidase activities were not affected.
Abstract: —Intraperitoneal injections of GABA (5 mg/kg) to rats lowered the level of norepinephrine in brain, heart and spleen but not suprarenals and raised that of serotonin in brain. Changes of these monoamines were most pronounced in the hypothalamic region after 20min. A reduction of hypothalamic norepinephrine was also observed 15min following the intracarotid administration of 0·5 mg/kg of GABA. In these experiments there was a concomitant increase in the level of free GABA in the anterior portion of the ventral hypothalamus. Brain dopamine level and 5-hydroxytryptophan decarboxylase, dihydroxyphenylalanine decarboxylase and monoamine oxidase activities were not affected. The 20 per cent increase of endogenous GABA observed in the midbrain 30 min following the administration of amino-oxyacetic acid was accompanied by a sharp fall in norepinephrine level (39 per cent) and an increase in serotonin (20 per cent).
In in vitro studies 10–300 μg/ml of GABA were shown to release norepinephrine from cortical and hypothalamic slices, and to inhibit serotonin release without affecting 5-hydroxytryptophan uptake and to have no effect on the release of dopamine from slices of the region of the corpus striatum nor on the activity of the enzymes mentioned.
Subcellular studies showed that the particulate:supernatant ratio for norepinephrine was reduced from a control value of 2·04 to 1·75 and that of serotonin was raised from 2·8 to 3·5. Following pretreatment with iproniazid, GABA reduced the raised level of brain norepinephrine to a greater extent than reserpine but not as intensively as amphetamine.
The results obtained suggest that these monoamines may be involved in the mechanisms underlying the action of GABA in brain and that the effect of GABA on brain monoamines may be of certain significance in synaptic events.
TL;DR: Immature rats maintained in a 14 :10 hr light: dark cycle, and sacrificed at 1:00 and 11:00 PM, showed a circadian rhythm in pineal serotonin levels, which is independent of sympathetic innervation.
Abstract: Immature rats (15–20 days) maintained in a 14 :10 hr light: dark cycle, and sacrificed at 1:00 and 11:00 PM, showed a circadian rhythm in pineal serotonin levels. When pineals of similar animals were sympathectomized by bilateral superior cervical ganglionectomy the serotonin rhythm persisted. Thus, in contrast to the adult, the serotonin rhythm in the immature pineal is independent of sympathetic innervation. At 60 days of age there was no rhythm in sympathectomized pineals; thus, the nerve dependent serotonin rhythm of the adultwas already established. When ganglionectomized immature rats were kept in constant light or in constant dark, the rhythm was abolished. Diurnal lighting, therefore, is important maintain the nerve independent serotonin rhythm of the immature rat. In contrast, the rhythm in the adult rat persists in constant dark. The mechanism controlling circadian serotonin rhythm in immature rats may be very different from that in adult animals. Ontogeny of the rhythm is proposed and discussed...
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