Showing papers on "Serotonin published in 1971"
TL;DR: Brain serotonin cocentrations at 1 p.m. were significantly elevated 1 hour after rats received a dose of L-tryptophan and 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.
Abstract: 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.
980 citations
TL;DR: 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, and serotonin-containing neurons may participate in systems whereby the rat brain integrates information about the metabolic state in its relation to control of homeostatis and behavior.
Abstract: 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.
688 citations
TL;DR: Data indicate that superior cervical sympathectomy abolishes the N-acetyltransferase rhythm by elimination of the input of central signals to the gland.
Abstract: There is a diurnal rhythm in the activity of serotonin N-acetyltransferase in the rat pineal gland. In the normal rat, the nocturnal enzyme activities are 15-to 30-fold greater than are daytime activities. This rhythm is abolished by decentralization or removal of the superior cervical ganglia, procedures that interrupt the only source of central neural input to the pineal gland. This effect of superior cervical sympathectomy on the N-acetyltransferase rhythm cannot be attributed to changes occurring in the denervated pineal parenchymal cells. When chronically denervated glands are placed in organ culture with norepinephrine, the neurotransmitter normally located in sympathetic terminals in the gland, N-acetyltransferase activity increases 10- to 20-fold. These data indicate that superior cervical sympathectomy abolishes the N-acetyltransferase rhythm by elimination of the input of central signals to the gland. These signals appear to regulate the N-acetyltransferase rhythm in the normal rat by regulation of the release of norepinephrine from the sympathetic terminals within the pineal gland.
257 citations
Journal Article•
TL;DR: The administration of d -amphetamine, dibutyryl cyclic adenosine monophosphate and lithium or the exposure to hot environmental temperature, conditions known to increase brain serotonin synthesis, increased tryptophan concentration in brain by more than 100%.
Abstract: The administration of d -amphetamine. reserpine, dibutyryl cyclic adenosine monophosphate and lithium or the exposure to hot environmental temperature, conditions known to increase brain serotonin synthesis, increased tryptophan concentration in brain by more than 100%. Brain tryptophan concentration was also markedly increased by phenmetrazine, phenelzine, dl -fenfluramine, bulbocapnine, γ-hydroxybutyrate and probenecid. On the other hand, p -chlorophenylalanine which inhibits serotonin synthesis decreased brain tryptophan level by about 50%. Morphine, apomorphine, chlorpromazine, α-methyltyrosine, haloperidol or exposure to cold environment did not change brain tryptophan level. Changes in tyrosine levels in brain were similar, but less pronounced than those of brain tryptophan. The increase in brain tryptophan could be dissociated from changes in plasma tryptophan and in body temperature. However, when body temperature rose above 40°C the rise in brain tryptophan was associated with a proportional rise in plasma tryptophan. Since the concentrations of tryptophan normally present in the mammalian brain are below the Km for tryptophan hydroxylase, all drugs capable of increasing tryptophan level in brain should also stimulate serotonin synthesis. Accordingly, treatments found to increase brain tryptophan level also increased that of brain 5-hydroxyindoleacetic acid. Tryptophan measurements in brain might be used in screening for drugs affecting serotonin turnover.
250 citations
Journal Article•
TL;DR: With this new procedure, it will be possible to either correlate animal behavior with the rate of amine formation in various brain structures or to study the effect of drugs on brain monoamine synthesis rates.
Abstract: After the i.v. injection of tritium-labeled l-tmyptOphan and l-tymosine into mats, the specific activity of both compounds in plasma declined multiphasically. The specific activity of norepinephrine, dopamine and serotonin in brainstem and tele-diencephalon increased rapidly, surpassed the specific activity of the precursor amino acids in about 50 minutes and then declined slowly approaching the amino acid values. Simple equations were derived to calculate synthesis rates from the changes in the specific activities of the amines and amino acids. The calculated mates are consistent with previously reported values. With this new procedure, it will be possible to either correlate animal behavior with the rate of amine formation in various brain structures or to study the effect of drugs on brain monoamine synthesis rates.
187 citations
TL;DR: In mice made aggressive by prolonged isolation, there is a decrease in brain serotonin turnover, while increased aggressiveness has been noted in cats and rats given p-chlorophenylalanine (PCPA), which inhibits serotonin synthesis.
Abstract: THERE is some doubt about the role of brain serotonin in aggression. In mice made aggressive by prolonged isolation, there is a decrease in brain serotonin turnover1, while increased aggressiveness has been noted in cats2 and rats3 given p-chlorophenylalanine (PCPA), which inhibits serotonin synthesis4, although the experiments with cats2 were not confirmed later5. Dominguez and Longo6 reported that PCPA attenuates irritability and viciousness in rats with septal lesions, and Welch and Welch7 observed decreased aggressiveness in isolated mice given PCPA. The explanation for these contradictory results may be that different models of aggression are not mediated through the same areas of the brain or by the same biochemical mechanisms.
167 citations
TL;DR: The hyperactivity and hyperpyrexia produced by l‐tryptophan in rats treated with a monoamine oxidase inhibitor was inhibited by chlorpromazine, and Pretreatment of rats with p‐chlorophenylalanine did not inhibit hyperactivity produced by 5‐MeODMT.
Abstract: Summary
1
The hyperactivity and hyperpyrexia produced by l-tryptophan in rats treated with a monoamine oxidase inhibitor was inhibited by chlorpromazine.
2
Chlorpromazine did not inhibit the increased rate of synthesis of brain 5-hydroxytryptamine (5-HT) produced by tryptophan loading.
3
Hyperactivity and hyperpyrexia were also produced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) in rats. Pretreatment with a monoamine oxidase inhibitor potentiated the hyperactivity response. Pretreatment of rats with p-chlorophenylalanine did not inhibit hyperactivity produced by 5-MeODMT.
4
Chlorpromazine inhibits hyperactivity caused by tryptophan or 5-MeODMT after monoamine oxidase inhibition either by competition with 5-HT or 5-MeODMT, respectively, at receptor sites or by physiological antagonism.
164 citations
Journal Article•
TL;DR: Repeated administrations of lithium salts to rats increased brain 5-hydroxyindoleacetic acid and brain serotonin by about 80% and brain tryptophan by about 70%, suggesting that this could be the mechanism by which lithium stimulates serotonin synthesis.
Abstract: Repeated administrations of lithium salts (Li2CO3 or LiCl, 60 and 85 mg/kg, respectively, twice a day for five days) to rats increased brain 5-hydroxyindoleacetic acid (5-HIAA) by about 80% and brain serotonin by 15 to 20%. The changes were not due to an inhibition of 5-HIAA transport from brain, but to an increase in the rate of synthesis of brain serotonin. Rate of serotonin synthesis was measured by multiplying the rate constant of 5-HIAA decline, after inhibition of monoamine oxidase, by the steady-state level of 5-HIAA. The calculation indicated that lithium increased the synthesis rate of brain serotonin by about 80%. Moreover, chronic treatment with lithium salts also increased the levels of brain tryptophan by about 70%, suggesting that this could be the mechanism by which lithium stimulates serotonin synthesis.
157 citations
TL;DR: It was found that p-CPA induced large and reproducible increases in locomotor activity in a variety of situations and this hyperactivity could be reversed by 5-hydroxytryptophan, a precursor of serotonin.
153 citations
TL;DR: Results indicate that projections of the midbrain raphe neurons, which are believed to account for the major portion of forebraibn serotonin, also contain the bulk of the enzyme tryptophan hydroxylase in the forebrain.
151 citations
TL;DR: Analysis of urinary and cerebrospinal fluid amine metabolites documented the metabolic effects of the compounds during periods of behavioral change and clearly altered mood and thought patterns in some patients, while L-tryptophan was less active.
Abstract: L-dopa and L-tryptophan, metabolic precursors of norepinephrine and serotonin respectively, and αMPT, a blocker of catecholamine synthesis, were administered to depressed and manic patients in an attempt to decrease their psychopathology and to test the monoamine theory of affective disorders. L-dopa and αMPT clearly altered mood and thought patterns in some patients, while L-tryptophan was less active. Analysis of urinary and cerebrospinal fluid amine metabolites documented the metabolic effects of the compounds during periods of behavioral change.
TL;DR: Rat brain has been found to contain two forms of monoamine oxidase: an enzyme highly sensitive to the inhibitor clorgyline that acted on tyramine and serotonin (Type A).
TL;DR: This report is the first to show that both α- and β-adrenergic stimulation can increase cyclic AMP levels, and it is hoped that this will help clarify the role of these receptors in the control of cyclic adenosine 3',5'-monophosphate levels.
TL;DR: The histochemical fluorescence of neurons in brainstem raphe nuclei which are presumed to contain serotonin is selectively and stereospecifically enhanced by L-tryptophan at doses that also produce an elevation in the concentration of serotonin.
Abstract: The histochemical fluorescence of those neurons in brainstem raphe nuclei which are presumed to contain serotonin is selectively and stereospecifically enhanced by L-tryptophan at doses that also produce an elevation in the concentration of serotonin However, contrary to our assumptions, the increase in raphe fluorescence is not prevented by p-chlorophenylalanine, an inhibitor of serotonin synthesis These results suggest that under some conditions derivatives of tryptophan other than, or in addition to, serotonin may be of significance in raphe neurons
TL;DR: P -chlorophenylalanine, a blocker of serotonin biosynthesis, caused strong excitatory effects on intracranial self-stimulation 3–7 days after treatment, incompatible with the adrenergic theory of reward which ignores serotonin.
TL;DR: Because of the similarities in embryological origins of the retina and pineal gland, the experiments reported here to examine the characteristics of the metabolism of serotonin by the rat retina were carried out.
Abstract: IN MAMMALS, hydroxyindole 0-methyl transferase (HIOMT; S-adenosylmethionine: N-acetylserotonin 0-methyl transferase; EC2.1.1.4), the enzyme responsible for the biosynthesis of melatonin and other endocrinologically active 5-methoxyindoles, has been reported to occur exclusively in the pineal gland (AXELROD and WEISSBACH, 1961). We have recently observed HIOMT activity in the retina of the rat (unpublished results). Because of the similarities in embryological origins of the retina and pineal gland (WURTMAN, AXELROD and KELLY, 1968), we carried out the experiments reported here to examine the characteristics of the metabolism of serotonin by the rat retina. Retinae of adult male Wistar rats were used. Pooled retinae from five animals were incubated in vitro with 2 pCi of serotonin [2-\"T]binoxalate (New England Nuclear Co., Boston, Mass; specific radioactivity, 15.3 mCi/rnmol) in 0.5 ml of 0.1 M-phosphate buffer (pH 7.9) containing: 125 mglucose; 30 mM-nicotinamide; 10 mwcysteine hydrochloride; 4 mM-MgC1, and 1 mM-EDTA. The incubations were carried out in a Dubnoff metabolic shaker for 4 h a t 37°C with air as the gas phase. A blank, containing no tissue, was included in each series of incubations. Portions of 20 pl of the incubation media plus 20 pl of a mixture (4 pg each) of authentic serotonin, 5-methoxyserotonin, 5-hydroxyindoleacetic acid, 5-methoxyindoleacetic acid, 5-hydroxytryptophol, 5-methoxytryptopho1, N-acetylserotonin and melatonin (K and K Laboratories, Plainview, N.Y.), were chromatographed in a bidimensional TLC system, as described by KLEIN and NOTIDES (1969). Precoated 10 x 20 cm plates (Silica Gel FZs4, E. Merck, A. G. Darmstadt, Germany) were activated at 110°C for 1 h and sprayed with 0.5 % (w/v) ascorbic acid in methanol before use. The plates were developed twice with chloroform-methanol-glacial acetic acid (93 :7: 1, by vol.), rotated through 90°, and developed
TL;DR: Rat pineal organs maintained in organ culture converted [ 14C]tryptophan to [14C]serotonin and [14 C]melatonin and the synthesis of both indoles was stimulated by the presence of norepinephrine or dibutyryl adenosine 3′,5′‐monophosphate.
Abstract: Rat pineal organs maintained in organ culture converted [14C]tryptophan to [14C]serotonin and [14C]melatonin. The synthesis of both indoles was stimulated by the presence of norepinephrine or dibutyryl adenosine 3′,5′-monophosphate. This effect of norepinephrine could be blocked by the α-adrenergic blocking drug, propranolol, but was not modified by the a-adrenergic blocking agent, phenoxybenzamine. Neither blocking agent modified the pineal response to dibutyryl adenosine 3′,5′-monophosphate. Unlike dibutyryl adenosine 3′,5′-monophosphate, the naturally occurring adenosine phosphates did not stimulate synthesis of [14C]melatonin in vitro.
TL;DR: The purpose of the experiments described here was to study the effect of p-chlorophenylalanine on heterosexual mounting behaviour in castrated males, which had been given a dose of testosterone adjusted to maintain a submaximal mounting response.
Abstract: EVIDENCE has accumulated that copulatory behaviour in the female and male rat is inhibited by increased central nervous serotoninergic tone1–4. One approach to the study of the specificity of the antagonistic relationship between serotonin and copulatory behaviour has been selectively to increase serotonin by the combination of a monoamine oxidase inhibitor and the serotonin precursor 5-hydroxytryptophane (5-HTP). B. J. M. has shown that this treatment inhibits the copulatory response (lordosis reflex) in the female rat4 and we have also shown3 it to decrease the number of male rats mounting oestrous females. Analogous experiments with the catecholamine precursor dihydroxyphenylalanine (DOPA) revealed no inhibitory effect of increased catecholamine concentrations. According to the studies of Shillito5,6 and Tagliamonte et al.7, a selective decrease of serotonin by the serotonin synthesis inhibitor p-chlorophenylalanine8 augmented sexual and social interaction between male rats, and in our work this agent also facilitated sexual receptivity in oestrogen-treated ovariectomized females9. Increased copulatory behaviour after p-chlorophenylalanine treatment has recently been shown in the male and female cat10,11, although contradictory results are also available12–14. The purpose of the experiments described here was to study the effect of p-chlorophenylalanine on heterosexual mounting behaviour in castrated males, which had been given a dose of testosterone adjusted to maintain a submaximal mounting response.
TL;DR: Norepinephrine synthesis in posterior hypothalamus and serotonin synthesis in both regions of the hypothalamus were similar in the two groups, and it was demonstrated that norepine cortisol synthesis was greater in the anterior hypothalamus of ovariectomized rats than in the posterior hypothalamic region of ovarian rats treated with 17β-estradiol and progesterone.
Abstract: A method is presented for determining the synthesis rate of norepinephrine and serotonin in anterior and posterior hypothalamus of rat from the changes of specific radioactivity of these amines and their respective precursor amino acids after an intraventricular injection of the radioactive amino acids. With our procedure we demonstrated that norepinephrine synthesis was greater in the anterior hypothalamus of ovariectomized rats than in the anterior hypothalamus of ovariectomized rats treated with 17β-estradiol and progesterone. Norepinephrine synthesis in posterior hypothalamus and serotonin synthesis in both regions of the hypothalamus were similar in the two groups. (Endocrinology 89: 1345, 1971)
TL;DR: Serotonin is present in several ganglia in Aplysia in concentrations of 2-4 gm/gm and is also present in the heart and during incubation of auricles in vitro serotonin-3H is concentrated tenfold from the medium.
Abstract: 1. Serotonin is present in several ganglia in Aplysia in concentrations of 2-4 gm/gm and is also present in the heart (0.6-1.3 μgm/gm).2. During incubation of auricles in vitro serotonin-3H is concentrated tenfold from the medium. This accumulation is inhibited by DMI, ouabain and Na + -free (TRIS) solutions. Ganglia incubated in vitro concentrate less serotonin-3H and at least a portion appears to be bound in non-nervous tissue.3. Dopamine is present in high concentration (24 /igm/gm) in some ganglia but is absent in others. There is a large amount of dopamine in the gill and the walls of the branchial vein, probably in sensory neurons.4. Although dopamine is not present in the auricle, it can be concentrated there, presumably in serotonergic neurons.
TL;DR: There is an inverse relationship between [3H]5‐HT accumulation and the endogenous 5‐HT level and the results are consistent with a negative feedback of 5‐ HT synthesis at the rate‐limiting tryptophan hydroxylation step.
Abstract: — The effect of increased levels of 5-hydroxytryptamine (5-HT) on the synthesis of [3H]5-HT from intracisternally injected tracer doses of [3H]tryptophan was studied in the rat brain stem. The [3H]5-HT which accumulated in the first 15 min after [3H]tryptophan injection was measured at various times after the acute intraperitoneal administration of the monoamine oxidase inhibitors Catron or Pargyline. The 5-HT levels reached two and three times control values respectively at 20 min and 180 min after monoamine oxidase inhibitor administration but [3H]5-HT accumulation was decreased (40 per cent) at 180 min when compared with 20 min. These data as well as those obtained after chronic treatment with monoamine oxidase inhibitors revealed that there is an inverse relationship between [3H]5-HT accumulation and the endogenous 5-HT level. Monoamine oxidase activity was undetectable during all the intervals in which [3H]5-HT accumulation was measured. No inhibition of [3H]5-HT accumulation was detected when [3H]5-hydroxytryptophan was injected instead of [3H]tryptophan. The results are consistent with a negative feedback of 5-HT synthesis at the rate-limiting tryptophan hydroxylation step.
TL;DR: It seems likely that physiological increases in intraneuronal tryptophan could drive the hydroxylation of the amino-acid and, ultimately, its conversion to serotonin.
Abstract: SEROTONIN, a putative neurotransmitter in the mammalian central nervous system, is synthesized in the brain by the 5-hydroxylation and decarboxylation of the essential amino-acid L-tryptophan1,2. The control of serotonin biosynthesis seems to involve a different mechanism from that responsible for catecholamine biosynthesis3,4 in its dependence on the availability of the amino-acid precursor5,6. Thus, small doses of tryptophan that do not increase brain or plasma tryptophan concentrations beyond their normal daily ranges cause significant increases in the serotonin concentration of rat brain7. Conversely, the chronic ingestion of diets lacking in tryptophan (with casein hydrolysates or amino-acid mixtures substituted for natural proteins) depresses brain serotonin levels8–10. The dependence of serotonin biosynthesis on tryptophan availability probably arises from the unusually high substrate K M that characterizes tryptophan hydroxylase1. It seems likely that this enzyme normally functions in an unsaturated state; hence physiological increases in intraneuronal tryptophan could drive the hydroxylation of the amino-acid and, ultimately, its conversion to serotonin.
TL;DR: Either caffeine prevents the release of brain serotonin or is able to increase serotonin synthesis, as indicated by the concentration of 5-hydroxyindole acetic acid in the brain indicating that caffeine did not prevent serotonin deamination by monoamine oxidase.
TL;DR: It is reported that various treatments which have been shown to increase brain serotonin synthesis also increase the concentration of tryptophan in brain, and p-chlorophenylalanine (PCPA), which inhibits serotonin synthesis3, decreases tryptophile in brain.
Abstract: THE concentrations of tryptophan normally present in the mammalian brain are below the Michaelis constant (Km) of tryptophan hydroxylase1,2, suggesting that the rate of serotonin synthesis depends more on the concentration of brain tryptophan than on the amount of enzyme. We wish to report that various treatments which have been shown to increase brain serotonin synthesis also increase the concentration of tryptophan in brain. Conversely, p-chlorophenylalanine (PCPA), which inhibits serotonin synthesis3, decreases tryptophan in brain.
TL;DR: L-Dopa, a precursor of dopamine, has been found to help patients suffering from this disease, presumably by increasing the concentration of dopamine in the brain.
Abstract: THE principal biochemical defect associated with Parkinsonism is a marked decrease in the dopamine and serotonin content of the brain1. L-Dopa, a precursor of dopamine, has been found to help patients suffering from this disease, presumably by increasing the concentration of dopamine in the brain2.
TL;DR: The current biological theories of depression are united in postulating a role for brain monoamine deficiency in this group of disorders, and several versions of the monoamine deficit theory of depression have been put forward with emphasis on one or other of these compounds.
Abstract: The current biological theories of depression are united in postulating a role for brain monoamine deficiency in this group of disorders. The relative importance of the various amines, dopamine (DA), norepinephrine ( NE ), serotonin (5–HT ) and tryptamine, is still unsettled, and several versions of the monoamine deficit theory of depression have been put forward with emphasis on one or other of these compounds.5, 56, 94, 128
TL;DR: The results confirmed that adrenergic nerves of golden hamster islets contain large amounts of norepinephrine, but none is visible in islets of albino rabbits and mice, and all three species had a similar in vitro sensitivity to the inhibition of insulin secretion by dopamine.
Abstract: Serotonin and dopamine are potent inhibitors of insulin secretion in the in vitro golden hamster pancreas system. In the present studies, the effects of serotonin and dopamine on insulin secretion in several species were investigated. In vivo glucose-stimulated insulin release was inhibited in white rabbits by constant infusion of serotonin (25 μg/min), and in white mice by an intravenous bolus of serotonin (0.25 mg). Whereas 5 × 10-5M serotonin inhibited glucosemediated insulin release from golden hamster pancreas in vitro, 2 × 10-3M serotonin was required to inhibit insulin release from pieces of rabbit or mouse pancreas. In contrast, all three species had a similar in vitro sensitivity to the inhibition of insulin secretion by dopamine. Histochemical studies have shown that adrenergic nerves of golden hamster islets contain large amounts of norepinephrine, but none is visible in islets of albino rabbits and mice. To determine if the increased susceptibility of the hamster pancreas to inhibition of insu...
TL;DR: It was confirmed that a circadian rhythm of spontaneous motor activity, and accordingly of the sleep-and-wakefulness pattern is formed gradually about 3 weeks after birth, and it was suggested that the maturation of circadian Rhythm of brain norepinephrine and serotonin contents is closely related with that of spontaneous activity and theSleep- and- wakefulness mechanism.
TL;DR: Yohimbine, 5 or 20 mg/kg given intraperitoneally, increased the concentration of brain serotonin and decreased that of 5-HIAA, in the rat and could be considered as a potential tool to test the involvement of serotoninergic processes in endogenous depression.