Showing papers on "Serotonin published in 1968"
Journal Article•
TL;DR: Changes in NE turnover regulation induced by electric foot shocks were studied in various conditions and there was an enhanced turnover of NE in the brainstem-mesencephalon when higher intensities of stimulation were used; this was associated with an increased accumulation of H 3 -normetanephrine.
Abstract: The effect of stress on the metabolism of norepinephrine (NE), dopamine and serotonin (5-hydroxytryptamine; 5HT) in the central nervous system of the rat has been examined. Estimations of turnover of NE have been made by following the changes in NE specific activity after labeling the endogenous stores of NE by intracisternal injection of H 3 -NE. Stress induced by mild electric shocks to the feet did not significantly affect the endogenous content of NE but did markedly increase the turnover of this amine in central NE-containing neurons, mainly in the brainstem-mesencephalon and in the spinal cord. The disappearance of H 3 -dopamine in the striatum and brainstem-mesencephalon was not affected under these conditions. This stress increased the synthesis of 5HT in the brainstem-mesencephalon as seen by the greater increase of endogenous 5HT after monoamine oxidase inhibition but did not affect the disappearance of intracisternally administered H 3 -5HT. Changes in NE turnover regulation induced by electric foot shocks were studied in various conditions. There was an enhanced turnover of NE in the brainstem-mesencephalon when higher intensities of stimulation were used; this was associated with an increased accumulation of H 3 -normetanephrine; no modification was seen when the frequency of stimulation was increased. NE turnover during an acute stress session was enhanced to a greater degree when rats were previously subjected to many stress sessions. The initial accumulation of H 3 -NE in the brainstem-mesencephalon was decreased just after an acute stress and increased 24 hr after the last electric shock stress session of a chronic stress treatment.
408 citations
TL;DR: An inhibition of neurons containing serotonin after administration of d-lysergic acid diethylamide could account for the decreased metabolism of serotonin produced by this drug.
Abstract: Units in areas of the midbrain rich in neurons containing serotonin respond to parenteral injections of d-lysergic acid diethylamide by a reversible cessation of spontaneous activity. The dose required is at or below threshold for gross behavioral effects. An inhibition of neurons containing serotonin after administration of d-lysergic acid diethylamide could account for the decreased metabolism of serotonin produced by this drug.
379 citations
Journal Article•
TL;DR: By various techniques it could be demonstrated that the stress of foot shock accelerates the metabolism of dopamine and serotonin to the same degree as norepinephrine; the only difference being that serotonin and dopamine are rapidly resynthesized, whereas nore Alpinephrine in the brain cannot be regenerated at the same rate.
Abstract: The stress of foot shock in rats induces large decreases in the level of brain norepinephrine but does not greatly alter the concentration of serotonin or dopamine in brain. These decrements in norepinephrine are not limited to any region and occur uniformly throughout the brain. However, absolute levels of these amines are not a true indicator of their dynamic state. By various techniques it could be demonstrated that the stress of foot shock accelerates the metabolism of dopamine and serotonin to the same degree as norepinephrine; the only difference being that dopamine and serotonin are rapidly resynthesized, whereas norepinephrine in the brain cannot be regenerated at the same rate. Furthermore, the increased catabolism of brain norepinephrine with stress is blocked by monoamine oxidase inhibitors, whereas catechol-O-methyltransferase inhibitors do not impede accelerated degradation.
291 citations
TL;DR: The intraperitoneal administration of melatonin to rats caused an increase in brain serotonin concentration, especially in the midbrain, which was demonstrated within 20 minutes ofmelatonin administration and was not associated with changes in norepinephrine concentration.
Abstract: The intraperitoneal administration of melatonin to rats caused an increase in brain serotonin concentration, especially in the midbrain. This effect could be demonstrated within 20 minutes of melatonin administration and was not associated with changes in norepinephrine concentration.
254 citations
235 citations
TL;DR: The formation of 3H-5HT from3H-TRY was significantly increased in the brain of stressed animals and the utilization of this labelled amine synthesized endogenously was markedly accelerated during the stress situation.
200 citations
TL;DR: Preference for ethyl alcohol was significantly reduced or totally abolished in rats given orally p-chlorophenylalanine, a tryptophan hydroxylase inhibitor that selectively depletes brain serotonin, and preference returned to normal as soon as α-methyl-p-tyrosine was terminated.
Abstract: Preference for ethyl alcohol was significantly reduced or totally abolished in rats given orally p- chlorophenylalanine, a tryptophan hydroxylase inhibitor that selectively depletes brain serotonin. Some aversion to alcohol was observed while p- chlorophenylalanine was administered, but the rats9 rejection of alcohol was even more marked after the drug was discontinued. Oral administration of α-methyl -p- tyrosine, a tyrosine hydroxylase inhibitor that depletes brain catecholamines, slightly reduced selection of alcohol, but preference returned to normal as soon as α-methyl -p- tyrosine was terminated.
149 citations
Journal Article•
TL;DR: Results indicated a close correlation between electrode placement and changes in indole levels in the forebrain, and suggests that there has been an upward adjustment in the rate of serotonin biosynthesis.
Abstract: The midbrain of rats was stimulated electrically in the region of the dorsal and mediati raphe via acutely placed electrodes, and parameters of stimulation were varied. In all animals, concentrations of serotonin and 5-hydroxyindoleacetic acid were measured in the forebrain, and sites of electrode placement in the brainstem were determined histologically. Results indicated a close correlation between electrode placement and changes in indole levels in the forebrain. Only in those regions of the midbrain with serotonin-containing itetirons did stimulation produce an increase in serotonin catabolism. There was a maximum change at a stimulus frequency of 10 pulses/sec. This amounted to a fall in serotonin of 18% and a rise in 5-hy- droxyindoleacetic acid of 80% with 1 hr of stimulation. The fall in serotonin reaches a maximum in the first 15 min. Thereafter, the concentration of serotonin does not change, while 5-hydroxyindoleacetic acid continues to rise. The fact that the serotonin concentration remains constant beyond 15 min, despite continued stimulation, suggests that there has been an upward adjustment in the rate of serotonin biosynthesis.
148 citations
TL;DR: The amount of time that monkeys (Macaca mulatta) slept was reduced after they were given p-chlorophenylalanine, a selective depletor of serotonin in animal tissues.
Abstract: The amount of time that monkeys (Macaca mulatta) slept was reduced after they were given p-chlorophenylalanine, a selective depletor of serotonin in animal tissues. The time spent in the rapid eye movement stage of sleep was unchanged, but the time in other sleep stages decreased. Seven regions of the brain had a 31 to 46 percent decrease in serotonin content; the concentration of cerebellar serotonin increased by 44 percent.
114 citations
TL;DR: In this paper, the authors examined the biosynthetic and metabolic pathways of the brain monoamines, NE, dopamine, and 5-HT by the characterization of the specific enzyme systems concerned in each step.
Abstract: Publisher Summary This chapter examines the biosynthetic and metabolic pathways of the brain monoamines, NE, dopamine, and 5-HT by the characterization of the specific enzyme systems concerned in each step. The enzyme in brain responsible for the hydroxylation of tryptophan to 5-HTP has recently been studied in several laboratories, and its existence is now firmly established. p -chlorophenylalanine ( p -CPA) in vitro inhibits tryptophan hydroxylation by enzyme systems capable of converting tryptophan to 5-HTP and exerts potent blockade in vivo of the liver enzyme and the brain enzyme. Inhibition of liver tryptophan hydroxylase in vitro by p -CPA or p -chlorophenylpyruvic acid is markedly decreased in the presence of 6,7-dimethyl-5,6,7,8-tetrahydropterin (DMPH), a synthetic cofactor. p -CPA fails to modify the symptomatic effects of reserpine-like drugs, and does not augment the slight sedation seen after nontoxic doses of a-methyltyrosine. p -CPA does give an indication of hyperalgesic activity, of blocking the analgesic action of morphine, of facilitating convulsions, and of antagonizing sleep. The compound also promises to be an excellent means of producing a model for phenylketonuria.
107 citations
TL;DR: The distribution of tryptophan hydroxylase in the cat brain was investigated and found to parallel roughly the distribution of serotonin.
Abstract: — The distribution of tryptophan hydroxylase in the cat brain was investigated and found to parallel roughly the distribution of serotonin. The most active areas are the caudate nucleus, septal area, anterior perforating substance, hypothalamus, amygdala and various areas of the midbrain.
TL;DR: It seems that restraint stress, which presumably imposes an increased demand for brain catecholamines and serotonin to maintain neurotransmission, rapidly activates a mechanism to conserve these amines and activates it to different degrees in mice which differ in emotional reactivity.
Abstract: THE relatively great reactivity of highly emotional animals must be correlated with neural function, but there seem to have been no previous reports of differential effects of stress on specific neurotransmitters in the brains of animals which differ in excitability. We have found that restraint stress can cause a greater elevation of brain catecholamines and serotonin in mice made hyperexcitable by 8–12 weeks of isolation than in their less excitable littermates housed in groups. This differential elevation of brain amines occurs in spite of the slower turnover of these neurotransmitters in isolated mice in normal non-stressed conditions1–3,6. Furthermore, after inhibition of catecholamine biosynthesis by α-methyltyrosine, stress facilitated the depletion of norepinephrine and dopamine in mice that had been kept isolated, but retarded their depletion in mice that had been housed in groups. It seems that restraint stress, which presumably imposes an increased demand for brain catecholamines and serotonin to maintain neurotransmission, rapidly activates a mechanism to conserve these amines and activates it to different degrees in mice which differ in emotional reactivity.
TL;DR: A new class of tryptophan hydroxylase inhibitors, the 6-halotryptophans, are described, which cause a greater drop in serotonin levels than does p-C1P for an equimolar dose and may have a more complicated action in vivo than the simple competitive inhibition demonstrated in vitro.
TL;DR: It is observed that isotopically labelled tryptophan as the substrate for organ culture preparations can transform the serotonin produced to two end products: 5-hydroxyindole acetic acid (5HIAA) and melatonin.
Abstract: Formation of melatonin and 5-hydroxy-indole acetic acid from C14 tryptophan by rat pineal glands in organ culture
TL;DR: The simultaneous incubation with serotonin and glucose led to a slight decrease in insulin release, which rose with increasing serotonin concentrations, and the insulin production induced by serotonin stimulation was quantitatively equivalent to the maximal amount of insulin released by 2 mg glucose per ml, and by 1 mg of tolbutamide per ml.
Abstract: Serotonin stimulated insulin release, independently of glucose, from rabbit pancreatic tissuein vitro. A concentration of 100 μg/ml gave a maximal insulin release. Higher concentrations delayed insulin release. —The simultaneous incubation with serotonin and glucose led to a slight decrease in insulin release. This decrease in insulin release rose with increasing serotonin concentrations. — The insulin production induced by serotonin stimulation (100 μg/ml) was quantitatively equivalent to the maximal amount of insulin released by 2 mg glucose per ml, and by 1 mg of tolbutamide per ml. — The significance of these findings with regard to the difference in the results obtained with the oral as compared with the intravenous glucose tolerance test, and with respect to the pathogenesis of both the dumping and the carcinoid syndromes were discussed.
TL;DR: Compound 51641 thus is a potent inhibitor of MAO in vitro and in vivo and was not reversible by dialysis and was independent of enzyme concentration.
TL;DR: Differences were found in the weight and the serotonin content of the forebrain, in the catecholamine contents of the brain stem and of the adrenal gland as well as in the Weight of the testis in male albino mice from two strains selectively bred for aggressiveness.
Abstract: Lagerspetz, K. Y. H., Tirri, R. & Lagerspetz, K. M. J. Neurochemical and endocrinological studies of mice selectively bred for aggressiveness. Scand.J. Psychol., 1968, g, 157–160.—Several neurochemical and endocrinological variables were studied in male albino mice from two strains, selectively bred for aggressiveness and non-aggressiveness. Differences were found in the weight and the serotonin content of the forebrain, in the catecholamine contents of the brain stem and of the adrenal gland as well as in the weight of the testis. The results indicate that mice selectively bred for aggressiveness show physiological signs of higher orthosympathetic activity than the mice selectively bred for non-aggressiveness.
TL;DR: Determination of serotonin and noradrenalin brain levels shows that ovulation is only affected by increased brain serotonin, and it is concluded that this amine has a specific inhibitory effect on the release of pituitary ovulation hormone.
TL;DR: Results indicate that after an initial decline in hypothalamic and amygdaloid level of serotonin, there followed a significant rise in this amine during the remaining period of exposure to aggression and defeat, supporting the ergotropic-trophotropic role attributed to these biogenic amines.
TL;DR: The experimental results of Sourkes and Poirie indicate that the course of striatopetal dopamine and 5-HT neurons of monkey and cat are similar to those of rat, which indicates that the function of the monoamine nerves in the corpus striatum is explained.
Abstract: Publisher Summary The chapter presents the experimental results of Sourkes and Poirie, which indicate that the course of striatopetal dopamine and 5-HT neurons of monkey and cat are similar to those of rat. In recent uptake experiments with brain slices, it has been observed that the axons after leaving the cell bodies of the pars compacta of the substantia nigra bend toward the medial lemniscus and the red nucleus before they become aggregated and take a ventral-rostral direction. The lesions producing contralateral hypokinesia and ipsilateral striatal dopamine loss reported by Sourkes and Poirier destroy the nigro-neostriatal pathway just after these fibers become aggregated. The function of the monoamine nerves in the corpus striatum by observing the asymmetries occurring after a unilateral lesion of the striatopetal monoamine pathways combined with drugs interfering with the monoamine metabolism is explained in this chapter. Injection of monoamine precursors produces a formation of amines in the caudal part of a transected cord and the functional changes occurring there cannot be because of an action of amines formed in other parts of the central nervous system. In rabbit and cat, the spinal effects elicited by 5-HTP and dopa are similar; therefore, in these two species it is not easy to determine the functional roles of 5-HT and NE neurons in the spinal cord. In the spinal rat, however, the two monoamine precursors produce different actions: dopa produces an increased flexor reflex whereas 5-HTP produces hyperextension, athetoid movements, and a weak tremor of about the same magnitude as that elicited in intact rats.
TL;DR: This chapter provides an account of the pharmacological experiments to study the relation between brain monoamine levels and fever in the rabbit, which states that the balance in the release of monoamines from the cells of the anterior hypothalamus is the mechanism whereby temperature is maintained and controlled.
Abstract: Publisher Summary This chapter provides an account of the pharmacological experiments to study the relation between brain monoamine levels and fever in the rabbit, which states that the balance in the release of monoamines from the cells of the anterior hypothalamus is the mechanism whereby temperature is maintained and controlled. The chapter also presents a relationship between the degree of hyperthermia caused by leukocytic pyrogen and the selective depletion of 5-HT by p -chlorophenylalanine or NE by α -methyl- p -tyrosine. An interesting finding is the potentiation of a leukocytic pyrogen fever in the rabbit following the injection of the precursor's 5-HTP and dopa. The results of microinjections into the anterior hypothalamus of a conscious monkey are presented. In rhesus monkey, a change in temperature depends critically on the dose of 5-HT injected into the third cerebral ventricle or anterior hypothalamus. The brain transfusion studies have revealed a number of facts, including the first direct evidence of a functionally specific release of transmitter substance from the central nervous system of a conscious animal.
TL;DR: The functional significance of brain 5-HT is reviewed and the function of brain NE may be inferred from the effects of free catecholamines released from normal sites of storage and protected from monoamine oxidase (MAO).
Abstract: Publisher Summary The discovery that reserpine impairs the storage of 5-HT and catecholamines has focused attention on the possible role of these biogenic amines in brain function and in mediating the pharmacologic and behavioral effects of the drug. This chapter reviews the functional significance of brain 5-HT. NE and 5-HT modulate opposing systems in the brain. The excitatory effects of 5-HTP have been used as a major argument against the view that 5-HT is the trophotrophic hormone. However, there is new evidence that these excitatory effects are caused through the release of NE. If only one of the amines is altered, the effects on physiologic behavior and EEG might suggest which neuronal pathway it modulates. The function of brain NE may be inferred from the effects of free catecholamines released from normal sites of storage and protected from monoamine oxidase (MAO). Reserpine in doses that reduce the brain levels of catecholamines and 6-HT by 55% produces obvious sedation and doses that decrease the levels by 70 to 80% evoke marked sedation and a syndrome of signs typical of trophotrophic stimulation including blepharospasm, extreme miosis, enhanced light reflex, diarrhea, and increased muscle tone.
TL;DR: The serum levels and diurnal rhythm of serotonin before and during treatment were investigated in 65 manic‐depressive patients, comparing with those in 34 normal controls and 13 schizophrenics.
Abstract: Summary
The serum levels and diurnal rhythm of serotonin before and during treatment were investigated in 65 manic-depressive patients, comparing with those in 34 normal controls and 13 schizophrenics.
1. The serum serotonin level in 40 newly admitted depressive patients who had not been medicated (127±58 ng/ml) was significantly lower than that in normal controls (221±96ng/ml).
2. The serum serotonin level in 24 recovering patients with depression had the tendency to return to normal while under treatment with imipramine type antidepressants (281±189 ng/ml).
3. The serum serotonin level in 10 manic patients (365±85 ng/ml) was significantly higher than that in normal controls.
4. After the injection of imipramine to depressive patients, serum serotonin level tended to increase (1.5 times).
5. Electroconvulsive shock did not appear to alter the serum serotonin level in depressive patients and normal dogs.
6. As for the diurnal rhythm of serum serotonin of depressive patients, the serotonin level in the morning was the lowest, which seemed to be related to the worst depressed mood in the morning. In the manic patients, the serotonin level at 20.00 hours was the highest. This pattern of rhythm resembled that of normal controls.
7. The significance of serum serotonin levels in manic-depressive patients was discussed.
TL;DR: Studies on the stimulus-induced release of exogenous 5-HT from molluscan tissues in vivo or in vitro and from mammalian brain in vitro provide additional support for the hypothesis that 5- HT may act as a transynaptic mediator in the mammalian central nervous system.
Abstract: Publisher Summary The chapter describes studies on the stimulus-induced release of exogenous 5-HT from molluscan tissues in vivo or in vitro and from mammalian brain in vitro. These data provide additional support for the hypothesis that 5-HT may act as a transynaptic mediator. Serotonin has been identified in the nervous system and other tissues in many classes of mollusks together with the enzymes for its synthesis and metabolism. 5-HT exerts a strong depolarizing and excitatory action upon specific molluscan neurons while serotonin antagonists such as lysergic acid diethylamide (LSD) and bromolysergic acid diethylamide (BOL) block the spontaneous excitatory synaptic potentials as well as the effect of iontophoretically applied 5-HT on these neurons. The chapter presents study on the sea hare, Aplysia californica, to obtain further evidence of the neurohumoral role of 5-HT in mollusks. It also presents studies on rat brain slices. The findings from these studies are similar to the results obtained with NE, and support the contention that 5-HT may serve as a synaptic mediator in the mammalian central nervous system.
TL;DR: The results suggest that the decrease in body temperature after the administration of harmaline may be the consequence of a disturbance of monoamine relationship at brain thermoreceptor sites.