Showing papers on "Serotonin published in 1984"
TL;DR: Do results mean that some serotonin-containing neurones play a role in the natural regulatory system which serves to match an organism’s nutritional intake to its bodily requirements?
560 citations
TL;DR: Ki's for blocking uptake of norepinephrine, serotonin, and dopamine into synaptosomal preparations of rat brain were determined for 25 antidepressants and putative antidepressants, some neuroleptics, stimulants, antihistamines and other monoamines to compare the relative potencies of a drug at the three processes.
548 citations
TL;DR: It was found that the CSF content of the major metabolite of serotonin, 5-hydroxyindoleacetic acid, was lower in depressed than in nondepressed parkinsonians, suggesting that the alterations in serotonin metabolism in Parkinson's disease identify a subgroup of patients who are prone to depression.
Abstract: Depression is a common symptom in patients with Parkinson's disease. It is not related to the severity of the motor symptoms or changes in dopamine metabolism and does not improve on treatment with dopamine agonists. Alterations in serotonin metabolism are found in primary (endogenous) depression. The brain content of serotonin in Parkinson's disease is also reduced, but this has not been related to any manifestation of the disorder. We found that the CSF content of the major metabolite of serotonin, 5-hydroxyindoleacetic acid, was lower in depressed than in nondepressed parkinsonians. The data suggest that the alterations in serotonin metabolism in Parkinson's disease identify a subgroup of patients who are prone to depression.
338 citations
Journal Article•
TL;DR: Compared the actions of ketanserin and pipamperone and metergoline and methysergide on two behavioral responses in rats that are produced by the activation of 5-HT receptors, the order of relative potency for these drugs to block the head shake response was the same as their reported affinity for the 5- HT2 receptor, which suggests that the5-HT2 receptor is involved in the headshake response.
Abstract: Ligand binding studies have identified certain serotonin (5-HT) antagonists with selective affinity for 5-HT2 receptors and other serotonin antagonists with affinity for both 5-HT1 and 5-HT2 receptors. This study compared the actions of ketanserin and pipamperone, selective 5-HT2 receptor antagonists, with metergoline and methysergide, nonselective 5-HT antagonists, on two behavioral responses in rats that are produced by the activation of 5-HT receptors: 1) the head shake response and 2) the 5-HT syndrome. Both the selective and the nonselective 5-HT antagonists blocked the head shake response produced by 5-hydroxy-L-tryptophan. The order of relative potency was: metergoline greater than ketanserin greater than pipamperone greater than methysergide. All four antagonists also blocked the head shake response produced by the 5-HT agonist quipazine. In contrast, the symptoms of the 5-HT syndrome produced by 5-methoxy-N,N-dimethyltryptamine were blocked by pretreatment with the nonselective 5-HT receptor antagonists but not by the 5-HT2 receptor antagonists. The differential actions of 5-HT antagonists on these behavioral responses suggest that different 5-HT receptors are involved in the head shake response and the 5-HT syndrome. That the order of relative potency for these drugs to block the head shake response was the same as their reported affinity for the 5-HT2 receptor suggests that the 5-HT2 receptor is involved in the head shake response. In contrast, the ability of 5-HT antagonists with affinity for the 5-HT1 receptor to block the 5-HT syndrome and the inability of 5-HT2 receptor antagonists to block the syndrome suggests that this behavioral response probably involves the activation of 5-HT1 receptors.
308 citations
TL;DR: In patients dying in hospital with depression, and in individuals committing suicide, there are no consistent changes in monoamine metabolites, and noradrenergic, serotonergic, and other neurotransmitter receptors were found to be unchanged, although there was a moderate decrease in imipramine binding in a small group of subjects with a history of depression.
296 citations
TL;DR: There was a marked blunting of the maximal prolactin response to the tryptophan in both the male and female patients, providing strong support for a possible serotonergic abnormality in depression.
Abstract: • There is considerable evidence that serotonergic function may be reduced in the brains of depressed patients. Serotonin is an effective stimulant of prolactin release, and intravenous (IV) tryptophan (the amino acid precursor of serotonin), when administered to healthy subjects, produces a reliable and robust increase in serum prolactin level. To evaluate serotonergic function in depressed patients, we gave 25 patients and 19 age- and sex-matched controls tryptophan, 7 g IV. There was a marked blunting of the maximal prolactin response to the tryptophan in both the male and female patients. The patient control differences could not be accounted for on the basis of age, sex, or time without medications. The data provide strong support for a possible serotonergic abnormality in depression.
276 citations
TL;DR: Electrophysiological evidence for decreased postsynaptic sensitivity to GABA following chronic benzodiazepine administration is presented as measured by the direct iontophoretic application of GABA and serotonin onto serotonergic cells in the midbrain dorsal raphe nucleus (DRN), known to receive GABAergic input.
Abstract: Benzodiazepines exert most of their pharmacological effects by a selective facilitation of the postsynaptic actions of GABA. Clinical, behavioural and electrophysiological studies have shown reduced drug response following chronic benzodiazepine administration. We present here electrophysiological evidence for decreased postsynaptic sensitivity to GABA following chronic benzodiazepine administration as measured by the direct iontophoretic application of GABA and serotonin onto serotonergic cells in the midbrain dorsal raphe nucleus (DRN), known to receive GABAergic input. The subsensitivity to GABA was found to be dose dependent and was seen when diazepam administration was three weeks or longer. Further, acute injection of the specific benzodiazepine antagonist, Ro15-1788, was found to reverse rapidly the decrease in GABA sensitivity observed in chronically diazepam-treated animals without altering GABA sensitivity in vehicle-treated rats. Decreased response to chronic benzodiazepines does not appear to be consistently related to alterations in the number or affinity of receptors for benzodiazepines. Our studies of radioligand-binding showed a decrease in the ability of GABA to enhance benzodiazepine binding in cerebral cortical membranes from chronic diazepam-treated animals without significant changes in benzodiazepine binding site density or affinity.
275 citations
TL;DR: It appears that several transmitters can converge to produce presynaptic facilitation in the sensory neurons of the defensive withdrawal reflex, and all of the transmitters studied here, the SCPs and serotonin, act via an identical molecular cascade.
Abstract: We have found that two endogenous neuropeptides in Aplysia, the small cardioactive peptides SCPA and SCPB, facilitate synaptic transmission from siphon mechano-sensory neurons and enhance the defensive withdrawal reflex that these sensory neurons mediate Single-channel recording revealed that these peptides close a specific K+ channel, the S channel, which is sensitive to cAMP Moreover, the peptides increase cAMP levels in these sensory neurons This reduction in K+ current slows the repolarization of the action potential in these cells, which increases transmitter release In these actions, the SCPs resemble both noxious sensitizing stimuli, which enhance the reflex, and serotonin Bioassay of HPLC fractions of abdominal ganglion extracts and immunocytochemistry indicate that both the SCPs and serotonin are present in the ganglion and are found in processes close to the siphon sensory neurons, suggesting that these transmitters may be involved in behavioral sensitization Recent evidence suggests that one group of identified facilitatory interneurons, the L29 cells, does not appear to contain either the SCPs or serotonin but may use yet another facilitatory transmitter Thus, it appears that several transmitters can converge to produce presynaptic facilitation in the sensory neurons of the defensive withdrawal reflex All of the transmitters studied here, the SCPs and serotonin, act via an identical molecular cascade: cAMP-dependent closure of the S-K+ channel, broadening of the presynaptic action potential, and facilitation of transmitter release
249 citations
TL;DR: Near-total dopamine-depleting brain lesions produced in 3-day-old rats by intracerebroventricular injection of the neurotoxin 6-hydroxydopamine led to pronounced increases in striatal serotonin (5-HT) and 5-hydroxyindoleacetic acid contents 1-8 months later, suggesting that proliferation of new serotonergic terminals had occurred within the striatum.
242 citations
TL;DR: Reversal potentials for serotonin and LSD-induced hyperpolarizations showed a shift of approximately 18 mV for a two-fold change in extracellular potassium concentration; this shift was close to that predicted by the Nernst equation for a potassium-dependent conductance.
TL;DR: The loss of S2 receptors in ATD may be a relatively early change in the disease process, and may precede the changes in ascending serotonergic neurones, as significant correlations were observed between S2 receptor binding and somatostatin immuno‐reactivity in temporal and frontal cortices.
Abstract: Serotonin receptors were assessed in post-mortem brains of control and Alzheimer-type dementia (ATD) patients using ligand binding techniques. Differential losses of serotonin S1 and S2 receptors were present in neocortex, hippocampus, and amygdala of ATD patients, whereas no significant changes were observed in basal forebrain and basal ganglia. Losses of S1 receptors were significantly age-related in the ATD group, suggesting they occurred at a later stage of the disease process. Losses of S2 receptors were considerably greater (with a reduction to 35% of control in temporal cortex) and were not age-related in ATD. Significant correlations were observed within the ATD group between S2 receptor binding and somatostatin immunoreactivity in temporal and frontal cortices. Thus the loss of S2 receptors in ATD may be a relatively early change in the disease process, and may precede the changes in ascending serotonergic neurones.
TL;DR: The results suggest that octopamine and serotonin have dual effects on posture: within the central nervous system, they act specifically to generate coordinated motor patterns for flexion or extension; as circulating neurohormones, they acts nonspecifically to enhance the responses of exoskeletal muscles to motoneuronal activation.
Abstract: Injection of the monoamines octopamine and serotonin into the hemolymph of lobsters causes them to assume opposing static postures: octopamine causes a tonic extension of all extremities, while serotonin induces a tonic flexion These amines have been shown previously to act as circulating neurohormones and to cause contraction of isolated exoskeletal muscles The opposing postures elicited by amine injection do not appear to arise from peripheral actions, however, since serotonin and octopamine have similar effects on both flexor and extensor muscles Instead, the amines are present within the central nervous system where they are probably released synaptically to activate coordinated patterns of tonic motor activity generating the observed postures These motor patterns have been recorded from abdominal ganglia and involve the synchronized activation and inhibition of multiple excitatory and inhibitory motoneurons innervating the postural flexor and extensor muscles These effects can be observed in an isolated abdominal ganglion To begin a search for the cellular targets of amine action within the central nervous system, we recorded from identified postural motoneurons in abdominal ganglia In two motoneurons that act to produce postural extension, octopamine reduced and serotonin raised the apparent threshold for action potential generation recorded in the somata The amines do not significantly affect the resting potential or input resistance of the motoneurons measured in the cell bodies Although the amine effect on motoneuron excitability could be due to actions directly on the motoneurons, our evidence suggests that at least part of the effect results from activation or inhibition of premotor interneurons: (1) an increase in EPSP frequency is observed in the motoneurons during octopamine superfusion, while a small decrease is observed during serotonin superfusion; (2) the amine effects on action potential threshold are abolished by cobalt ion These results suggest that octopamine and serotonin have dual effects on posture: within the central nervous system, they act specifically to generate coordinated motor patterns for flexion or extension; as circulating neurohormones, they act nonspecifically to enhance the responses of exoskeletal muscles to motoneuronal activation
TL;DR: An investigation of 5HT stimulated phosphatidylinositol (PI) hydrolysis in rat cerebral cortex is reported and it is found that selective 5HT-2 antagonists (pizotifen and ketanserin) block 5HT's effect upon PI metabolism.
TL;DR: It is concluded that PAT is a potent 5-HT agonist acting on both post- and presynaptic 5- HT receptors in the rat brain.
01 Jul 1984-Journal of Comparative Physiology A-neuroethology Sensory Neural and Behavioral Physiology
TL;DR: Serotonin is localized to a limited population of identifiable neurons in the C.N.S., and plays a pivotal and mandatory role in organizing the feeding behavior of the medicinal leech.
Abstract: 1.
We have investigated functional roles of serotonin (5-hydroxytryptamine, 5-HT) in the feeding behavior of the medicinal leech,Hirudo medicinalis. Bathing intact leeches in serotonin (3×10−5 mol/l, 20 min) significantly alters three components of their feeding behavior. Leeches exposed to serotonin initiate swimming toward a vibrating point with a shorter latency, bite a warm surface more frequently, and ingest more blood than control animals.
2.
Thermal stimulation of the prostomium evokes pharyngeal peristalsis, jaw movements and an obvious salivation by semidissected preparations. The application of serotonin (10−8 to 10−6 mol/l) directly activates and increases the rates of pharyngeal peristalsis and salivary secretion in these preparations. Serotonin also produces jaw movements and a constriction of the crop when centrally applied.
3.
Vibrational stimuli, which evoke the swimming phase of feeding behavior, synaptically excite Retzius cells within segmental ganglia. Thermal stimuli, which evoke the biting phase, synaptically excite 5-HT-containing neurons within the subesophageal ganglia. Intracellular stimulation of identified 5-HT-containing neurons produces pharyngeal peristalsis reliably and enhances salivation.
4.
Pharmacological lesions of particular 5-HT neurons abolishes feeding behavior. However, a brief exposure to exogenous 5-HT restores biting behavior. Well-fed leeches do not normally bite, but a brief bath in 5-HT will evoke biting behavior by them as well.
5.
Serotonin is localized to a limited population of identifiable neurons in the C.N.S., and plays a pivotal and mandatory role in organizing the feeding behavior of the medicinal leech.
TL;DR: The results indicate that 5-HT2 receptors show different pharmacological profiles in different species, and caution should be exerted in extrapolating data from laboratory animals to humans.
TL;DR: Results of this investigation are consistent with electrophysiologic and behavioral studies in laboratory rats and suggest that desipramine- and amitriptyline-induced alterations in 5-HT function may be related to their antidepressant mechanism of action.
Abstract: • The effects of amitriptyline hydrochloride and desipramine hydrochloride treatment on brain serotonin (5-HT) function were investigated in 21 patients. The ability of an intravenous infusion of the serotonin precursor tryptophan to raise serum prolactin (PRL) levels was determined in 13 depressed patients during placebo administration and after 28 to 35 days of treatment with either amitriptyline or desipramine. Both desipramine (N = 7) and amitriptyline (N =6) significantly increased the PRL rise induced by tryptophan compared with a preceding placebo period. In contrast, following long-term amitriptyline and desipramine treatment, the ability of tryptophan to increase PRL was enhanced two weeks following abrupt cessation of amitriptyline therapy (N= 5), but not after discontinuation of desipramine therapy. The results of this investigation are consistent with electrophysiologic and behavioral studies in laboratory rats and suggest that desipramine- and amitriptyline-induced alterations in 5-HT function may be related to their antidepressant mechanism of action.
TL;DR: The reduction in serotonin receptors did not correlate with a clinical assessment of the degree of dementia, or with the extent of Alzheimer-type neuropathological change, and a selective loss of serotonergic binding sites characterised as both S1 and S2 sites was observed.
TL;DR: Serotonin-S2 sites were demonstrated to have a role in serotonin-induced behavioural excitation in rodents and they probably mediate perception of subjective feelings elicited by serotonin mimetics, and platelets proved to be an integral model for studying serotonin-S1 sites.
Journal Article•
TL;DR: The present results do not support the previously proposed idea that in nerve terminals a functional coupling may exist between uptake mechanisms and presynaptic receptors.
Abstract: The possibility of interaction between neurotransmitter uptake mechanisms and presynaptic receptors regulating transmitter release was investigated using rat brain synaptosomes in superfusion. Various conditions were considered including: absence of substrate for the uptake with uptake potentially operative; absence of substrate and presence of uptake inhibitors; and uptake activated by added substrate, with or without uptake inhibitors. The release of [3H]-5-hydroxytryptamine ([3H]-5-HT) evoked by 15 mM KCl from cerebral cortex synaptosomes was inhibited by lysergic acid diethylamide. The 5-HT uptake inhibitors citalopram and chlorimipramine did not affect the inhibitory action of lysergic acid diethylamide. Clonidine decreased both the K+-evoked release of [3H]norepinephrine and that of [3H]-5-HT in cortical synaptosomes through the activation of presynaptic alpha-2 adrenoceptors. In superfusion conditions, the action of clonidine on [3H]norepinephrine release was not antagonized by the norepinephrine uptake inhibitors desipramine or cocaine; similarly, the inhibition of [3H]-5-HT release was unaffected when 5-HT uptake was blocked. The K+-evoked release of [3H]dopamine from striatal nerve terminals was potentiated by acetylcholine (ACh) through the activation of muscarinic presynaptic receptors. The action of ACh was not modified by the presence of nomifensine, a dopamine uptake inhibitor. Finally, in superfused cortical synaptosomes, the block of the high-affinity uptake of choline by hemicholinium-3 had no effect on the muscarinic autoreceptor-mediated inhibition of [3H]ACh release by ACh. Altogether the present results do not support the previously proposed idea that in nerve terminals a functional coupling may exist between uptake mechanisms and presynaptic receptors.
TL;DR: The possibility is discussed that the availability of cyclic AMP through serotonin activation in these parasites may be a prelude to the development processes that take place in the parasite.
Abstract: It is evident from the above review that during the last two decades a great deal of interest in investigating the action of serotonin in parasitic worms has been shown by parasitologists as well as by scientists from several other disciplines What we have initially reported concerning the effect of serotonin on motility and carbohydrate metabolism of F hepatica has been pursued on several other parasitic worms The studies so far indicate that serotonin stimulates motility of every species tested among the phylum Platyhelminthes The indoleamine also stimulates glycogenolysis in the few flatworm parasites that have been investigated The information in nematodes is scanty and the role of serotonin in these parasites is still open for experimentation Recent biochemical investigations on F hepatica and S mansoni demonstrated that serotonin and related compounds utilize a common class of receptors in plasma membrane particles which I designate as 'serotonin receptors' These receptors are linked to an adenylate cyclase that catalyses the synthesis of the second messenger, cyclic 3',5'-AMP Serotonin and its congeners increase the concentration of cyclic AMP in intact parasites whereas antagonists inhibit such an effect Cyclic AMP stimulates glycogenolysis, glycolysis and some rate-limiting glycolytic enzymes It activates a protein kinase that may be involved in activation of glycogen phosphorylase and phosphofructokinase Serotonin-activated adenylate cyclase in S mansoni is activated early in the life of the schistosomule The possibility is discussed that the availability of cyclic AMP through serotonin activation in these parasites may be a prelude to the development processes that take place in the parasite The different components of the serotonin-activated adenylate cyclase in the parasite are the same as those that have been previously described for the host Binding characteristics of the receptors indicate that the receptors in F hepatica appear to be different from those that have been described in the host The discovery of these receptors and their differences from those in the host offer a new site which is amenable to pharmacological manipulation The search for new agents that influence serotonin receptors in these parasites could be included in a strategy for the development of new chemotherapeutic agents against these parasites
TL;DR: Evidence is provided for a functional role as true receptor initiating a physiological response of the 5-HT2 receptor on human platelets and for the potency of these compounds correlates strongly with their potential to inhibit the specific binding of ketanserin.
TL;DR: These studies show that several piperazine-containing compounds can evoke a potent release of endogenous stores of hypothalamic 5-HT in vitro, actions which should be considered together with their direct agonist activity when interpreting the CNS effects in vivo.
TL;DR: Serotonin assays of known cholinergic neurons that were covered by immunoreactive fibers indicated that measurable amounts of serotonin were associated with such neurons, but the concentration of serotonin was an order of magnitude lower than in neurons known to stain with the anti-serotonin serum.
TL;DR: Quantitation of grains in specific regions of the intermediate gray revealed that alpha 2-adrenergic and serotonergic receptors were more highly concentrated over sympathoadrenal preganglionic neurons than over other regions in IML or the adjacent intermediate gray matter.
Abstract: Receptor autoradiography was combined with the retrograde labeling of sympathoadrenal neurons by fast blue to determine whether opiate, serotonin, catecholamine, or cholinergic binding sites could be spatially correlated with preganglionic neurons in the rat intermediolateral cell column (IML) that project to the adrenal gland. [3H]Dihydromorphine (DHM) was used for the visualization of mu opiate receptors, [3H]lysergic acid diethylamide (LSD) for serotonin receptors, [3H]para-aminoclonidine (pAC) for alpha 2-adrenergic receptors, and [3H]quinuclidinyl benzilate (QNB) for muscarinic cholinergic receptors. While qualitative assessment of autoradiograms indicated that alpha 2-adrenergic and muscarinic receptors were concentrated in the intermediate zone of the spinal cord, quantitation of grains in specific regions of the intermediate gray revealed that alpha 2-adrenergic and serotonergic receptors were more highly concentrated over sympathoadrenal preganglionic neurons than over other regions in IML or the adjacent intermediate gray matter. Information concerning the distribution of neurotransmitter-binding sites in other regions of thoracic spinal cord was also obtained. All ligands showed relatively dense binding sites in the superficial laminae of the dorsal horn, and all but [3H]DHM revealed similar densities of binding sites in the region adjacent to the central canal. Only [3H]QNB revealed a high density of binding sites in the ventral horn of the spinal cord.
TL;DR: It is demonstrated that serotonin both inhibits neutral sodium chloride absorption and stimulates active chloride secretion by a calcium-dependent process in the rat colon.
TL;DR: While hypothalamic histamine had the highest turnover rate, the rate constant for histamine in this region was among the lowest in brain, perhaps consistent with the presence of histaminergic cell bodies.
TL;DR: Results are consistent with the hypothesis that lithium carbonate may enhance serotonin (5-HT) receptor sensitivity, whereas TCA and second-generation antidepressants diminish 5-HT receptor sensitivity and the enhancement of the cortisol response to 5-htP by MAO inhibitors may be due to decreased metabolism of 5- HT.
Abstract: • Serum cortisol levels were significantly increased following administration of 5-hydroxytryptophan (5-HTP), 200 mg orally, to patients with affective disorders. A three-to five-week period of treatment with lithium carbonate or monoamine oxidase (MAO) inhibitor augmented the mean 5-HTP-induced increase in serum cortisol concentration in manic or depressed patients, respectively: tricyclic antidepressant (TCA) and second-generation antidepressant treatment diminished the mean serum cortisol response in patients with major depression. These results are consistent with the hypothesis that lithium carbonate may enhance serotonin (5-HT) receptor sensitivity, whereas TCA and second-generation antidepressants diminish 5-HT receptor sensitivity. The enhancement of the cortisol response to 5-HTP by MAO inhibitors may be due to decreased metabolism of 5-HT. It is important to assess the effect of thymoleptic drug treatment on various responses to biogenic amine precursors or agonists in patients rather than laboratory animals.
Journal Article•
TL;DR: The present results suggest that enhancement of serotonergic neurotransmission might mediate the therapeutic effect of both types of treatment in major depression.
Abstract: Electroconvulsive therapy remains one of the most effective treatments of major depression. The effect of electroconvulsive shocks (ECSs) on the responsiveness of hippocampal pyramidal neurons to serotonin, norepinephrine, gamma-aminobutyric acid and 5-methoxydimethyltryptamine was studied in rats pretreated with one or six ECSs. Control rats were given subconvulsive shocks. Microiontophoretic experiments were conducted 36 hr after the last shock in urethane-anesthetized or low cerveau isole preparations. Responsiveness of hippocampal pyramidal neurons to microiontophoretic applications of serotonin was markedly enhanced in rats pretreated with six ECSs. Responsiveness to 5-methoxydimethyltryptamine, a postsynaptic agonist which is not an adequate substrate for the high-affinity serotonin reuptake process, was also enhanced in rats pretreated with six ECSs, indicating that the increased responsiveness to serotonin was due to a postsynaptic modification. The effects of norepinephrine and of gamma-aminobutyric acid applied on the same neurons were not modified by repeated ECS pretreatment. A single ECS failed to modify responsiveness to either serotonin or 5-methoxydimethyltryptamine. Inasmuch as long-term tricyclic antidepressant drug administration has been shown to produce a similar sensitization to serotonin, the present results suggest that enhancement of serotonergic neurotransmission might mediate the therapeutic effect of both types of treatment in major depression.