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Showing papers on "Serotonin published in 1970"


Journal Article
TL;DR: The results support the view that 6-hydroxydopamine produces a "central sympathectomy" when introduced into cerebrospinal fluid.
Abstract: After the intracisternal administration of 6-hydroxydopamine, brain levels of norepinephrine were reduced significantly with or without pargyline pretreatment. Depletion of dopamine in the central nervous system was found to be enhanced markedly by pargyline administration at higher dose levels of 6-hydroxydopamine. Brain serotonin concentrations were not altered. The effects of 6-hydroxydopamine were long-lasting with the depletion of brain amines persisting at 78 days. After norepinephrine-H3 intracisternally to animals treated with 6-hydroxydopamine, labeled norepinephrine uptake was diminished with a corresponding reduction of deaminated catechols and a marked increased in methylated amines. Tyrosine hydroxylase activity was found to be reduced in brainstem, caudate nucleus and whole brain in 6-hydroxydopamine-treated animals. Conversion of tyrosine-H3 to labeled norepinephrine and dopamine was also markedly diminished. The results support the view that 6-hydroxydopamine produces a “central sympathectomy” when introduced into cerebrospinal fluid.

518 citations


Journal ArticleDOI
15 May 1970-Science
TL;DR: 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 that apparently results from a release or displacement of serotonin from its storage sites.
Abstract: 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.

349 citations


Journal ArticleDOI
02 Oct 1970-Science
TL;DR: Observations support the hypothesis that a portion of exogenously administered L-dopa may enter central serotonin terminals and undergo decarboxylation to the amine with resultant displacement of the endogenous indoleamine from vesicular stores.
Abstract: L-Dopa markedly increased the efflux of tritiated dopamine and tritiated serotonin from rat brain slices. This action appeared contingent on the decarboxylation of L-dopa to dopamine, since it could be blocked by an inhibitor of L-amino acid decarboxylase. Selective destruction of catecholamine-containing nerve terminals by 6-hydroxydopamine significantly decreased the uptake and release of tritiated dopamine but not that of tritiated serotonin. These observations support the hypothesis that a portion of exogenously administered L-dopa may enter central serotonin terminals and undergo decarboxylation to the amine with resultant displacement of the endogenous indoleamine from vesicular stores.

346 citations


Journal ArticleDOI
TL;DR: Tryptophan 5-monooxygenase activity is detected in both the soluble and particulate fractions from the guinea pig brain stem and the radioactive CO2 evolved is almost entirely accounted for by the formation of serotonin-14C.

294 citations


Journal ArticleDOI
TL;DR: It is suggested that serotonin and acetylcholine play a role as initiators for different types of morphogenetic cell movements in the sea urchin embryo.

159 citations


Journal ArticleDOI
TL;DR: Five healthy volunteers given L-tryptophan for ten consecutive nights had an increase in non-rapid-eye-movement sleep (non-R.E.M.M.) and delta wave sleep while they manifested a decrease in R.E-M.

137 citations


Journal ArticleDOI
TL;DR: The results suggest that the serotonin concentration may be related to the process of sexual differentiation of the brain, since this concentration is modified by the same procedures that induce androgenization.
Abstract: Serotonin concentration was determined in the brains of male and female rats on the 1st, 4th, 8th, and 12th day after birth. It was observed that while the amount of 5HT is comparable within the two sexes up to day 8, it rises significantly in females on day 12. This elevation in serotonin levels could be prevented if the females were injected with testosterone propionate on the day of birth. By comparison, males castrated at birth had brain serotonin levels comparable to those in intact females and significantely greater than those in intact littermates. These results suggest that the serotonin concentration may be related to the process of sexual differentiation of the brain, since this concentration is modified by the same procedures that induce androgenization. It is also suggested that the testosterone liberated by the neonatal gonad may modify the metabolism of brain serotonin only on day 12, which period corresponds to the time of the sexual differentiation of the structures that control gonadotrophin secretion.

135 citations



Journal ArticleDOI
31 Jan 1970-Nature
TL;DR: There is strong evidence that the amine acts as a transmitter on one particular type of neurone in the gastropod brain and the precise type of particle or particles associated with serotonin is not definitely known.
Abstract: KNOWLEDGE of the subcellular localization of serotonin (5-hydroxytryptamine) in neurones is important for an understanding of the precise physiological role of this amine in nervous tissue. Some of the most pertinent pharmacological and electrophysiological data on the neuronal role of serotonin have been obtained from work with molluscs1,2. In particular there is strong evidence that the amine acts as a transmitter on one particular type of neurone in the gastropod brain2. Fractionation studies with homogenates of bivalve ganglia, which are extremely rich in serotonin, have shown that the amine is bound to particles, but associated with particles of different density from those binding acetylcholine3. The precise type of particle or particles associated with serotonin, however, is not definitely known4.

115 citations



Journal ArticleDOI
TL;DR: Pretreatment of rats with lithium chloride increased the rate of brain serotonin turnover and was accentuated by electrical stimulation of serotonincontaining neuronal perikarya in the dorsal raphe nucleus.

Journal ArticleDOI
TL;DR: It is suggested that diazepam may act on mechanisms subserving the transport of 5-HIAA from brain as well as on the cerebral metabolism of5-HT, a monoamine which is not metabolized in brain.

Journal ArticleDOI
10 Jul 1970-Science
TL;DR: The conversion index in the brainstem of adrenalectomized rats is smaller than in the same area of sham-operated rats, which suggests that in brainstem the decrease of tryptophan hydroxylase is reflected by the conversion index estimation and not by measurement of serotonin steady-state concentrations.
Abstract: Rats were adrenalectomized 10 days before we estimated in vivo the conversion index of 3H-tryptophan into radioactive serotonin in brainstem and telediencephalon. We found that the conversion index in the brainstem of adrenalectomized rats is smaller than in the same area of sham-operated rats. Conversely, the conversion index in the telediencephalon was similar in the two groups of rats. The serotonin concentrations were unchanged by adrenalectomy, which suggests that in brainstem the decrease of tryptophan hydroxylase is reflected by the conversion index estimation and not by measurement of serotonin steady-state concentrations.

Journal ArticleDOI
TL;DR: The increased turnover of serotonin in PS-deprived animals appeared to be related to the impossibility of triggering PS, and the utilization of brain serotonin endogenously synthesized from [ 3 H]tryptophan was accelerated during PS deprivation.


Journal ArticleDOI
TL;DR: If the platelet is a valid model for dopaminergic brain neurones, then the results described would suggest that dopamine uptake and storage may be abnormal inbrain neurones in Parkinson's disease.
Abstract: 1. Human blood platelets have been shown to take up dopamine by an energy-dependent, saturable process that is inhibited by 5-hydroxytryptamine (5-HT), desipramine and other drugs. 2. Platelets from parkinsonian subjects receiving oral L-DOPA also took up dopamine. 3. When the responses of normal and parkinsonian platelets were compared, the parkinsonian cells showed the following differences: increased affinity for the dopamine transport process; decreased equilibrium concentrations of dopamine after incubation for 90 min, and greater efflux of dopamine from loaded platelets during a 10 min incubation. 4. There were no differences in the uptake of 5-HT by parkinsonian platelets, but endogenous 5-HT was significantly reduced; ATP was normal. 5. In two out of three samples of platelets from parkinsonian subjects, traces of a dopamine-like substance were detected, but this finding requires confirmation. 6. If the platelet is a valid model for dopaminergic brain neurones, then the results described would suggest that dopamine uptake and storage may be abnormal in brain neurones in Parkinson's disease.

Journal ArticleDOI
06 Feb 1970-Science
TL;DR: Serotonin in millimolar concentrations was toxic to fibroblasts and the two functional groups of the serotonin molecule were required for growth enhancement.
Abstract: 5-Hydroxytryptamine (serotonin) in micromolar amounts increased the growth of fibroblasts in culture while not affecting five other cell lines. Serotonin appeared to shorten the lag phase of cell growth. The effect was less when serotonin was added to the fibroblast culture after the initial 24-hour period. The two functional groups of the serotonin molecule were required for growth enhancement. Serotonin in millimolar concentrations was toxic to fibroblasts.


Journal ArticleDOI
TL;DR: Histochemical evidence suggests that neurons in the brain stem raphé nuclei which contain serotonin (5-HT) project to the spinal cord, and antagonists appear to act at the spinal level, presumably blocking the effect of a 5-HT-releasing interneuron intercalated in the bulbospinal inhibitory pathway.
Abstract: Histochemical evidence suggests that neurons in the brain stem raphe nuclei which contain serotonin (5-HT) project to the spinal cord. Stimulation of the raphe nuclei facilitated and inhibited spinal reflexes: the conduction velocity calculated for the bulbospinal inhibitory pathway was 10 m/sec. Antagonists of 5-HT were without effect on facilitation, but readily blocked raphe-evoked inhibition of the monosynaptic reflex. The antagonists also blocked the inhibition evoked from the ventral medial reticular formation. Blockade of bulbospinal inhibition was observed after LSD (0.25 mg/kg), methysergide (0.5 mg/kg), BOL (1–1.5 mg/kg) and cinanserin (4 mg/kg) but not cyproheptadine (5 mg/kg). The 5-HT antagonists were more effective when injected into the arterial supply of the spinal cord than when injected into the arterial supply of the brain stem. Thus, the antagonists appear to act at the spinal level, presumably blocking the effect of a 5-HT-releasing interneuron intercalated in the bulbospinal inhibitory pathway.

Journal Article
TL;DR: It is concluded that p -chloroamphetamine impairs the synthesis of cerebral 5-HT, and the results of these studies in vivo implicate an inhibition of cerebral tryptophan hydroxylase in the simultaneous lowering of cerebral5-HT and 5-hydroxyindole acetic acid by p - chloroamphetamine.
Abstract: The present investigations were undertaken to study the mechanism by which p -chloramphetamine decreases both serotonin (5-HT) and 5-hydroxyindole acetic acid in the brains of rats. 1) Doses of p -chloroamphetamine, which markedly reduced the level of endogenous 5-HT in brain, failed to decrease labeled 5-HT derived from either intraventricularly administered 5-HT-H 3 or 5-hydroxytryptophan-C 14 . Under similar conditions, reserpine and RO 4-1284 caused a striking reduction of both the endogenous and the labeled 5-HT. 2) p -Chloroamphetamine partially blocked the increase of endogenous brain 5-HT but not that of brain norepinephrine, after monoamine oxidase inhibition by pargyline. 3) The increase in brain 5-hydroxyindole acetic acid resulting from the administration of probenecid was almost completely blocked in animals treated 48 and 24 hours previously with p -chloroamphetamine. This blockade was not evident when p -chloroamphetamine was administered 10 minutes prior to probenecid. 4) Like p -chlorophenylaline, p -chloroamphetamine caused a decrease in the amount of 5-HT-C 14 in brain formed from intraventricularly administered tryptophan-C 14 ; however, it did not change the amount of 5-HT-C 14 derived from intraventricular 5-hydroxytryptophan-C 14 5) p -Chloroamphetamine did not alter the level of either endogenous tryptophan or tryptophan-C 14 taken up into the brain from the ventricular system. On the basis of these experimental data, it is concluded that p -chloroamphetamine impairs the synthesis of cerebral 5-HT. Moreover, the results of these studies in vivo implicate an inhibition of cerebral tryptophan hydroxylase in the simultaneous lowering of cerebral 5-HT and 5-hydroxyindole acetic acid by p -chloroamphetamine.

Journal ArticleDOI
TL;DR: Serotonin may have a role as a physiological inhibitor of insulin secretion in some species and this work has suggested that golden hamster pancreas has some species difference.
Abstract: To assess the possible functional role of serotonin on insulin secretion, pieces of golden hamster pancreas were incubated in a modified Krebs-Ringer bicarbonate buffer. In 10-4M concentration, serotonin suppressed basal insulin secretion and also insulin secretion that was stimulated by high glucose, tolbutamide, or dibutyryl cyclic AMP. Inhibition of insulin secretion by serotonin occurred over the entire range examined (1.0×10-4 to 5.8 ×10-4M). In a similar in vitro system, concentrations of serotonin as high as 5.8 ×10-4M were without significant effects on basal or high glucose (3 mg/ml) stimulated insulin release from mouse pancreas. Thus, serotonin effect on the pancreatic β cell has some species difference. Serotonin may have a role as a physiological inhibitor of insulin secretion in some species. (Endocrinology 86: 66, 1970)


Journal ArticleDOI
TL;DR: Measurement of amine levels suggested that catecholamine depletion was more influential at increasing the self-timulation threshold than serotonin depletion, and data suggest that both catecholicamines and serotonin are involved in pathways for self-stimulating drive-reward.

Book ChapterDOI
TL;DR: The studies on subcortical control of forebrain amine metabolism reviewed in the chapter provide a firm foundation for understanding the interdependent participation of cortical and sub cortical structures in the mediation of complex functions.
Abstract: Publisher Summary This chapter investigates the effects of subcortical lesions on brain serotonin levels to provide a correlation for the behavioral effects and the responses to drugs. The studies described in the chapter utilize the techniques of localized tissue destruction in the central nervous system to define the specific neuronal elements with which the biogenic monoamines, serotonin, norepinephrine, and dopamine are associated in the brain. The changes in behavior noted with the two effective lesions, septal and dorsomedial tegmental, combined with the alteration in sleeping time suggest a possibility that the effects of the lesions might be related to a change in the cerebral metabolism of the amine serotonin. The sedative effect of reserpine is related to decreases in brain serotonin, and it is proposed that this amine represents a central neurotransmitter, possibly mediating parasympathetic activities, such as sleep. Amine metabolism plays only a part in functions, for example, in the maintenance of food and water intake, but the studies on subcortical control of forebrain amine metabolism reviewed in the chapter provide a firm foundation for understanding the interdependent participation of cortical and subcortical structures in the mediation of complex functions.

Journal ArticleDOI
TL;DR: The bovine pituitary organ and median eminence contain large amounts of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and monoamine oxidase, which are greatest in the infundibular process.
Abstract: Serotonin, 5-hydroxyindoleacetic acid /5-HIAA/ and monoamine oxidase in bovine pituitary organ and median eminence

Journal ArticleDOI
TL;DR: The data does not support the idea that the effect of lysergic acid diethylamide is mediated through an increase in serotonin levels although the effects on carbohydrate metabolism of both agents are similar.

Journal ArticleDOI
TL;DR: 5-Hydroxy- l -tryptophan (5-HTP) has been found in high concentration in the mature seeds of Griffonia simplicifolia, a West African legume of reputed physiological activity, and in lower concentration in other parts of the plant.

Journal ArticleDOI
01 Jul 1970-Diabetes
TL;DR: The data indicate that both amines block insulin release by interfering with the action of 3′5′ cyclic AMP in causing insulin release.
Abstract: Similarities and differences in the mechanisms by which epinephrine and serotonin inhibit insulin secretion were studied in an in vitro golden hamster pancreas system. Both amines were shown to inhibit the insulin release stimulated by either high glucose (3 mg./ml.) or dibutyryl cyclic AMP 1 mg./ml. The beta adrenergic blocking agent propranolol had no effect on either basal or high glucose-stimulated insulin release. It also was without effect on the serotonin inhibition of high glucose-stimulated insulin release. Phentolamine, an alpha adrenergic blocking agent, prevented the serotonin inhibition of high glucose or dibutyryl cyclic AMP mediated insulin release. Phentolamine also blocked the action of epinephrine in inhibiting dibutyryl cyclic AMP mediated insulin release. The data indicate that both amines block insulin release by interfering with the action of 3′5′ cyclic AMP in causing insulin release. Phentolamine appears to act at the same locus, i.e., in the action of 3′5′ cyclic AMP. The only difference noted between serotonin and epinephrine action on the pancreatic beta cell was that methysergide maleate, a known serotonin antagonist, was able to block serotonin action but not that of epinephrine.

Journal Article
TL;DR: Serotonin appears to contract the blood vessels by a direct mechanism, similar to how cocaine potentiated serotonin-evoked contractions but not those to epinephrine or norepinephrine.
Abstract: The effects of drugs on spirally cut strips of sheep umbilical blood vessels were studied. Muscle activity was recorded isotonically. Serotonin, angiotensin and ergot alkaloids were found to be potent agonists. Maximal contractions to acetylcholine, epinephrine and norepinephrine were less than those to serotonin. The contractile responses to epinephrine and norepinephrine were blocked by alpha adrenergic blocking agents, whereas atropine blocked the response to acetylcholine. Contractions produced by serotonin were blocked by 2-bromolysergic acid diethylamide (BOL-148) but not by atropine, morphine or alpha adrenergic blocking agents. Cocaine potentiated serotonin-evoked contractions but not those to epinephrine or norepinephrine. Thus, serotonin appears to contract the blood vessels by a direct mechanism. The relaxations of ergotamine-contracted strips by isoproterenol and epinephrine were antagonized by propranolol. Evidence was obtained for the presence of both alpha and beta adrenergic receptors.

Journal ArticleDOI
TL;DR: The effect of AMTP on the concentration of serotonin and its acid metabolite 5H I M (5-hydroxyindolylacetic acid) in the brain is assessed and the availability of the separate isomers of AM TP enabled us to determine the contribution of each to this effect, as well as to other actions of the compound.
Abstract: SINCE 1956 when AMTP (a-methyltryptophan) was shown to stimulate the activity of tryptophan pyrrolase (tryptophan oxygenase; EC 1.13.1.12) in rat liver (SOURKES and TOWNSEND, 1955), this compound has been used in many biochemical experiments on the metabolism of tryptophan. The increased pyrrolase activity evoked by AMTP is analogous to that brought about by the administration of tryptophan (KNOX and MEHLER, 1950) in that it is manifested in adrenalectomized rats (CIVEN and KNOX, 1960) just as in intact animals. However, activation by tryptophan is short-lived, whereas the increased enzymic activity following a single injection of AMTP lasts for many days (SANKOFF and SOURKES, 1962). Chronic elevation of hepatic pyrrolase could lead to a relative deficiency of the indispensable amino acid tryptophan (MADRAS and SOURKES, 1965), and this could affect the formation of important compounds derived from it, namely, tryptamine, serotonin, melatonin and NAD, as well as many proteins. In this paper the effect of AMTP on the concentration of serotonin and its acid metabolite 5H I M (5-hydroxyindolylacetic acid) in the brain is assessed. The availability of the separate isomers of AMTP enabled us to determine the contribution of each to this effect, as well as to other actions of AMTP.