SEARCH · PubMed Health

Results for “Dihydroxytryptamines”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources

PubMed1984

In vivo increase in hypothalamic cyclic AMP following 5-hydroxytryptophan administration in rats.

The administration of 5-hydroxytryptophan (5-HTP, 100 mg/kg, i.p.) consistently increased hypothalamic cyclic AMP levels in rats treated 10 days earlier with the serotonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), to produce 5-HT receptor supersensitivity. However 5-HTP (100 mg/kg), failed to cause an increase in hypothalamic cyclic AMP in rats not pretreated with 5,7-DHT. The 5-HTP-induced increase in cyclic AMP was blocked by the decarboxylase inhibitor, benserazide (RO 4-4602, 800 mg/kg) and by the 5-HT antagonist metergoline (5 mg/kg). Other treatments that caused a significant elevation of hypothalamic cyclic AMP included: (a) L-Tryptophan plus the monoamine oxidase inhibitor, tranylcypromine, and (b) the serotonin agonist, 1-(m-trifluromethylphenyl)-1-piperazine. The 5-HT antagonist, methysergide, blocked the serotonin receptor mediated behavioral syndrome, but failed to prevent the increase in hypothalamic cyclic AMP. Moreover, the 5-HT agonist, 5-methoxy-N, N-dimethyltryptamine, (5-Me-DMT), induced a strong behavioral syndrome but failed to significantly increase hypothalamic cyclic AMP. These findings suggest that activation of 5-HT receptors somewhere in the brain causes an increase in hypothalamic cyclic AMP, but further studies will be needed to determine whether this is a direct result of activation of the 5-HT receptors in the hypothalamus.

5,7-Dihydroxytryptamine↗

PubMed1986

Studies on the separate roles of forebrain and spinal serotonin in morphine analgesia.

5,7-Dihydroxytryptamine (5,7-DHT) injections in the ventromedial tegmentum (VMT) at the level of nucleus interpeduncularis or in the ventral raphe area (VR) of the medulla oblongata were used to study the separate roles of forebrain and spinal 5-HT in the antinociceptive effect of morphine in rats. 5,7-DHT injections in the VMT, which caused marked, selective depletion of forebrain 5-HT, did not modify the effect of morphine in the hot plate and tail immersion tests. Direct injection of 5,7-DHT into the nucleus raphe medianus also failed to modify the effect of morphine in the two tests used to measure nociceptive responses. The effect of morphine was significantly reduced 30 min after injection to rats depleted of spinal 5-HT by 5,7-DHT injected in the VR but the areas under the curves between vehicle and 5,7-DHT treated animals were not significantly different. The data show that the integrity of 5-HT neurons in the forebrain is not necessary for the antinociceptive effect of morphine and a substantial amount of this effect is still present in rats with marked depletion of spinal 5-HT.

5,7-Dihydroxytryptamine↗

PubMed1984

Evidence that the dorsal raphe area is involved in the effect of clonidine against pentylenetetrazole-induced seizures in rats.

Injections of 5,7-dihydroxytryptamine (5,7-DHT) in the rat ventromedial tegmentum, which depleted forebrain serotonin, and of 6-hydroxydopamine in the dorsal noradrenergic bundle, which caused a marked reduction of forebrain noradrenaline, intensified pentylenetetrazol (PTZ)-induced seizures. Neither condition significantly modified the inhibitory effect of 0.5 mg/kg clonidine on PTZ-induced seizures, with the exception of the effect on mortality which was reduced in 5,7-DHT treated animals. Electrolytic lesions in the nucleus raphe medianus or dorsalis potentiated PTZ-induced seizures but only lesions in the nucleus raphe dorsalis significantly attenuated the effect of clonidine on tonic seizures and mortality. Both lesions reduced clonidine's effect on latency to the first convulsion. The results indicate that the dorsal raphe area plays a role in the inhibitory effect of 0.5 mg/kg clonidine on PTZ-induced seizures. Serotonin neurons other than those innervating diencephalic and telencephalic structures may also contribute, particularly to the effect of clonidine on tonic seizures.

5,7-Dihydroxytryptamine↗

PubMed1983

Studies on the role of serotonin in different regions of the rat central nervous system on pentylenetetrazol-induced seizures and the effect of di-n-propylacetate.

5,7-Dihydroxytryptamine (5,7-DHT) injections which caused selective depletion of serotonin in the forebrain enhanced the seizures caused by pentylenetetrazol (PTZ 90 mg/kg s.c.) in rats. No effect was observed in rats with 5,7-DHT-induced depletion of spinal serotonin or treated with metergoline (1 mg/kg i.p.) or methysergide (10 mg/kg i.p.). The various procedures aimed at decreasing serotonin transmission did not significantly modify the effect of di-n-propylacetate (DPA) on tonic seizures and mortality caused by PTZ but significantly reduced the DPA-induced increase in the latency to the first convulsion. More animals with clonic seizures were seen in the DPA-treated group which had been subjected to selective depletion of spinal serotonin or treated with methysergide than in DPA-treated controls. Combined treatment with d-fenfluramine (1.25 mg/kg i.p.) and DPA (75 mg/kg i.p.), doses which by themselves had no significant effect, reduced tonic seizures and mortality caused by PTZ. The results show that a diffuse deficit in forebrain serotonin enhances PTZ-induced seizures. Serotonin does not play an important role in the effect of DPA against PTZ-DPA on clonic convulsions. Agents increasing serotonin transmission may enhance the anticonvulsant activity of DPA.

5,7-Dihydroxytryptamine↗

PubMed1985

Lesioning of serotoninergic and noradrenergic nerve fibres of the rat brain does not decrease binding of 3H-clonidine and 3H-rauwolscine to cortical membranes.

alpha 2-Adrenoceptors located presynaptically on nerve terminals are known to modulate the release of neurotransmitters from noradrenergic and serotoninergic neurons. The pre- and/or postsynaptic localization of binding sites for alpha 2-adrenergic radioligands, the agonist 3H-clonidine and the antagonist 3H-rauwolscine, was investigated in the rat cerebral cortex by the use of specific neurotoxins. Intracerebroventricular injections of 6-hydroxydopamine (6-OH-DA) and 5,7-dihydroxytryptamine (5,7-DHT) were used to destroy the noradrenergic and serotoninergic neurons, respectively, and the success of the treatment was controlled by measurement of tritium accumulation in cortex slices incubated with 3H-noradrenaline or 3H-serotonin. In cortical membranes, 3H-rauwolscine bound to a single site (KD about 5 nmol/l; Bmax 217-247 fmoles/mg protein), whereas 3H-clonidine bound to a high affinity site (KD 0.6-1.4 nmol/l) and a low affinity site (KD 6-10 nmol/l). The total number of high plus low affinity 3H-clonidine binding sites was about two thirds of the number of 3H-rauwolscine binding sites. 6-OH-DA treatment significantly increased the number of high affinity 3H-clonidine binding sites without reducing the number of high plus low affinity binding sites, indicating a denervation supersensitivity. KD- as well as Bmax-values for 3H-rauwolscine remained unaltered after 6-OH-DA-treatment. Since an increase in postsynaptic alpha 2-adrenoceptors due to 6-OH-DA-administration might have masked a loss of presynaptic alpha 2-adrenergic binding sites, rats were chronically treated with high doses of clonidine in order to prevent a possible supersensitivity of postsynaptic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

PubMed1984

Clonidine-induced hypothermia: possible involvement of cholinergic and serotonergic mechanisms.

The thermoregulatory effects (including metabolic, vasomotor and respiratory activities) produced by an injection of clonidine (1-3 micrograms in 0.5 microliter) into the preoptic anterior hypothalamus were assessed in conscious rats at ambient temperatures (Ta) of 8, 22 and 30 degrees C. Intrahypothalamic administration of clonidine caused a dose-dependent fall in rectal temperature at Ta 8 degrees C and 22 degrees C. The hypothermia in response to clonidine was due to decreased metabolic heat production and/or cutaneous vasodilation. There was no change in respiratory evaporative heat loss. The clonidine-induced hypothermic response was attenuated by pretreatment of the rats with either 5,7-dihydroxytryptamine (10 micrograms, administered intrahypothalamicly, 14 days before clonidine injection), yohimbine (0.2 microgram, administered intrahypothalamicly, 10 min before clonidine injection), cyproheptadine (1 microgram, administered intrahypothalamicly, 10 min before clonidine injection), or atropine (0.1 microgram, administered intrahypothalamicly, 10 min before clonidine injection). The data indicate that clonidine may act on alpha-adrenoceptors located on a serotonin-acetylcholine pathway within the preoptic anterior hypothalamus to induce hypothermia by promoting a reduction in metabolic heat production and/or an enhancement in dry heat loss in rats.

5,7-Dihydroxytryptamine↗

PubMed1985

Immunohistological studies of masked indoleamine cells in the area postrema of the rat.

Masked indoleamine cells (MICS) in the area postrema and adjacent areas in the rat were immunohistochemically studied (the peroxidase-antiperoxidase method) using a serotonin antiserum. After pretreatment with nialamide (200-300 mg/kg), immunoreactive MICS could be observed. They were small cells (about 12 micron in diameter) with several processes and were distributed in nearly all parts of the area postrema and also in the nucleus tructus solitarii. Following a single intraventricular injection of 75 micrograms 5,6-dihydroxytryptamine, the immunoreactivity of these cells conspicuously decreased for several days. The submicroscopical structure of the cells was investigated using immunoelectron microscopy. Immunoreactive products were observed in the cytoplasm as particles with a diameter of 25-40 nm and high electron density, but these were not found in the nucleus or cell organelles.

5,6-Dihydroxytryptamine↗

PubMed1986

Differentiation of pre- and post-synaptic high affinity serotonin receptor binding sites using physico-chemical parameters and modifying agents.

The two 3H-labeled agonists [3H]8-hydroxy-2-(di-n-propylamino) tetralin ([3H]8-OH-DPAT) and [3H]serotonin ([3H]5-HT) have been used to examine the effects of physico-chemical parameters and modulatory agents on the high affinity 5-HT receptor binding sites in various regions of the rat central nervous system. Sites labeled by [3H]8-OH-DPAT and [3H]5-HT were differentially sensitive to changes in incubation temperature and pH, such that the optimal interaction of [3H]8-OH-DPAT with specific sites in the striatum was at 30 degrees C and pH 7.4, whereas [3H]5-HT sites in the same region were most easily labeled at 2-23 degrees C and pH 8.2. Micromolar concentrations of Mn2+ enhanced [3H]5-HT binding but inhibited markedly [3H]8-OH-DPAT binding to striatal membranes. In contrast, both [3H]5-HT and [3H]8-OH-DPAT binding were increased by the cation in hippocampal membranes. Conversely, GTP reduced the binding of either ligand in the hippocampus but affected only [3H]5-HT binding in the striatum. Furthermore, N-ethylmaleimide inhibited equally [3H]5-HT and [3H]8-OH-DPAT binding to hippocampal membranes, but was markedly less potent against [3H]8-OH-DPAT binding to striatal membranes. These results led to the definition of assay conditions for studying separately [3H]8-OH-DPAT binding to "hippocampal-like" (HL) and "striatal-like" (SL) sites. [3H]8-OH-DPAT HL binding sites were particularly abundant in the hippocampus, septum and cerebral cortex, and exhibited pharmacological properties typical of the postsynaptic 5-HT1A subsites previously characterized with [3H]5-HT as the ligand. The regional distribution of [3H]8-OH-DPAT SL binding sites was strikingly different from that of HL sites, but similar to that of serotoninergic terminals identified by their capacity to take up [3H]5-HT. The selective lesion by 5,7-dihydroxytryptamine of serotoninergic projections induced a marked loss of [3H]8-OH-DPAT SL binding sites in the striatum and the cerebral cortex, indicating that these sites were located presynaptically. In contrast, [3H]5-HT binding sites remained unchanged in lesioned rats, which confirmed further their exclusive postsynaptic location in brain.

5,7-Dihydroxytryptamine↗

PubMed1993

Independent effects of cholinergic and serotonergic lesions on acetylcholine and serotonin release in the neocortex of the rat.

Rats received a unilateral lesion of the nucleus basalis magnocellularis (NBM) by infusion of ibotenic acid. In addition, the dorsal raphe nucleus was lesioned by infusion of 5,7-dihydroxytryptamine (5,7-DHT). The release of acetylcholine (ACh), choline, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) was measured in the frontal neocortex by means of microdialysis. Lesions of the NBM, but not the raphe nucleus, reduced the release of ACh significantly (-47%). The release of 5-HT and 5-HIAA was reduced by raphe lesions (-44% and -79%+), but not by NBM lesions. In no case did the combined lesion affect neurotransmitter release more than a single lesion. These results suggest that serotonergic projections from the dorsal raphe nucleus are not involved in tonic inhibition of ACh release in the neocortex.

5,7-Dihydroxytryptamine↗

PubMed1992

Some regional anatomical relationships of TRH to 5-HT in rat limbic forebrain.

It is now a recognized principle that various neuropeptides are neuronally co-localized with biogenic amine or aminoacid neurotransmitters. In the rat CNS it has previously been shown that TRH is co-localized with 5-HT (and also with substance P) in cell bodies of the posterior raphe that project to the spinal cord. Although TRH cell bodies are known to be widely distributed throughout the forebrain there is no other known co-localization with 5-HT. In this study we further specify the forebrain there is no other known co-localization with 5-HT. In this study we further specify the anatomical relationship of TRH with 5-HT by use of surgical and neurotoxic lesioning with reference to limbic forebrain regions wherein TRH is greatly increased following seizures. In groups of rats, the fimbria-fornix was lesioned alone, or combined with a lesion of the dorsal perforant path or the ventral perforant path. There was a sham lesioned control group. Additional groups were lesioned with 5,7 dihydroxytryptamine, 100 micrograms i.v.t., 45 min. after i.p. desipramine, 25 mg/kg. All rats were sacrificed three weeks after lesions. Indoleamines were determined by HPLC in left anterior cortex, left pyriform/olfactory cortex, left dorsal hippocampus and left ventral hippocampus. TRH was determined by specific RIA in the corresponding right brain regions. The modal n was 7 rats.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

PubMed1992

Serotonin fiber innervation of cerebellar cell suspensions intraparenchymally grafted to the cerebellum of pcd mutant mice.

One aspect of integration of implanted neurons into the neuronal circuitry of a defective host brain is the re-establishment of a host-to-graft afferent innervation. We addressed this issue by using the adult cerebellum of 'Purkinje cell degeneration' (pcd) mutant mice, which lack virtually all Purkinje cells after postnatal day (P) 45. Purkinje cells constitute one of the cerebellar cell types being innervated by axons of raphé serotonin (5-HT) neurons. In normal mice, 5-HT-immunoreactive fibers are distributed to all cerebellar folia. Following Purkinje cell loss in pcd mice, cerebellar 5-HT-immunoreactive fibers persist. Cerebellar cell suspensions were prepared from embryonic day (E) 11-13 normal mouse embryos and were intraparenchymally grafted into the cerebellum of pcd mutants either directly or after pre-treatment with 5,7-dihydroxytryptamine (5,7-DHT) to selectively remove 5-HT cells of donor origin. The state of Purkinje cells and 5-HT axons was monitored in alternate sections by 28-kDa Ca(2+)-binding protein (CaBP) and 5-HT immunocytochemistry, respectively. Serotonin-immunoreactive axons were seen in the grafts from 5 to 32 days after transplantation. In some of the grafts which had not been pre-treated with 5,7-DHT, a small number of 5-HT-immunoreactive cell bodies was found, indicating that part of the 5-HT fiber innervation of the graft could actually derive from donor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

PubMed1994

Dissociation of the plasticity of 5-HT1A sites and 5-HT transporter sites.

To study the early effects of neonatal 5,7-dihydroxytryptamine lesions on 5-hydroxytryptamine1A (5-HT1A) receptors, we measured regional [3H]8-OH-DPAT-labeled 5-HT1A sites in binding assays and compared them to our previous studies of [3H]paroxetine-labeled 5-HT transporter sites during the first month in the same rats. While there were significant time- and dose-dependent effects of 5,7-DHT on 5-HT transporter sites, there were no significant changes in 5-HT1A sites in cortex, hippocampus, diencephalon, brainstem, cerebellum, or spinal cord. 5,7-DHT lesions also did not alter the Ki of Gpp(NH)p at brainstem 5-HT1A sites or the Ki of 5-HT in cortex or brainstem in the presence or absence of GTP gamma S or Gpp(NH)p. There were significant regional differences between the density of 5-HT1A sites and 5-HT transporter sites. The ontogeny of brainstem 5-HT1A sites was a pattern of increases until three weeks postnatal, and 5,7-DHT lesions did not alter the ontogeny of 5-HT1A sites. These data suggest differential plasticity of 5-HT1A and 5-HT transporter binding sites during the first month after neonatal 5,7-DHT lesions.

5,7-Dihydroxytryptamine↗

PubMedDate not supplied

Influence of local injection of 5,7-DHT and 6-OH-DA into the neocortex on learning and exploratory behavior of rats in the open field.

The features of the exploratory behavior in the open field, of the learning of a conditioned-reflex food-procuring reaction, and of the shift in the level of biogenic amines of the brain was studied in Wistar rats with local injections of the specific neurotoxins 6-hydroxydopamine (6-OH-DA) and 5,7-dihydroxytryptamine (5,7-DHT). It was shown that damage to the structure of the serotoninergic or catecholaminergic systems of the frontal cortex and hippocampus caused by local injection of 6-OH-DA and 5,7-DHT into the neocortex is accompanied by multidirectional changes in the exploratory behavior and learning of the animals.

5,7-Dihydroxytryptamine↗

PubMedDate not supplied

Interaction of serotonin- and dopaminergic systems of the brain in mechanisms of latent inhibition in rats.

The activity of serotoninergic neurons of the medial raphé nucleus was turned off by local injection of the neurotoxin, 5,7-dihydroxytryptamine. Seven days later, a conditioned passive avoidance reaction was developed following 20 preexposures to the conditional stimulus (the presentation of the experimental chamber). As compared with the sham-operated control, in which 20 preexposures to the stimulus elicited latent inhibition, i.e., attenuation of the reproduction of the conditioned passive avoidance reaction, prolonged maintenance at the formed level, and lack of susceptibility to amnesia, all of the enumerated features were disturbed in animals administered the neurotoxin. The administration of haloperidol (0.5 mg/kg) 1 h prior to training reestablished the state of latent inhibition which had been disrupted by the switching off of the mesolimbic serotonin system. It is hypothesized that the process of the suppression of attention to the nonreinforced signals during the preexposure to the stimulus is achieved by the interaction of the serotoninergic and dopaminergic systems.

5,7-Dihydroxytryptamine↗

PubMed1991

Role of presynaptic serotonergic receptors on the mechanism of action of 5-HT1A and 5-HT1B agonists on masculine sexual behaviour: physiological and pharmacological implications.

In order to establish whether the 5-HT1A or the 5HT1B agonists, 8-OH-DPAT or TFMPP, produce their facilitatory or inhibitory actions on masculine sexual behaviour via a mechanism involving: (a) the serotonin synthesis or release; (b) the stimulation of presynaptic receptors, or (c) the stimulation of somatodendritic receptors, three series of experiments were performed. The administration of the serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA, 300 mg/kg x 3 days), facilitated sexual behaviour but does not interfere neither with the inhibitory nor with the facilitatory effects of TFMPP (0.5 mg/kg) or 8-OH-DPAT (0.5 mg/kg), respectively. The icv or the intraraphé administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), slightly stimulated masculine sexual behaviour and produced a decrease in serotonin and its metabolite levels. In lesioned animals TFMPP (0.5 mg/kg) resulted in an inhibitory effect reflected as a prolongation of the ejaculation latency. The inhibitory effect of this drug on mounting behaviour was not observed in 5,7-DHT treated rats. In lesioned animals 8-OH-DPAT (0.5 mg/kg) produced the same facilitatory effect. Present data indicate that serotonergic postsynaptic receptors mediate both the inhibitory and the facilitatory actions of TFMPP or 8-OH-DPAT in copulation. All data further support the idea that endogenous serotonin acts via the stimulation of 5-HT1B receptors to induce its inhibitory effects on masculine sexual behaviour.

5,7-Dihydroxytryptamine↗

PubMed1991

Effect of chronic administration of antidepressant drugs on 5-HT2-mediated behavior in the rat following noradrenergic or serotonergic denervation.

Chronic (14 day) administration of several pharmacologically-distinct antidepressant drugs resulted in marked reductions in the serotonin2 (5-HT2)-mediated quipazine-induced head shake response which were accompanied by significant reductions in the density of cortical beta-adrenergic and 5-HT2 binding sites. Noradrenergic (DSP4[N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine]-induced) and serotonergic (5,7-DHT[5,7-dihydroxytryptamine]-induced) lesions either attenuated or blocked antidepressant-induced reductions in 5-HT2-mediated behavior. DSP4- and 5,7-DHT lesions did not alter the down-regulation of 5-HT2 binding sites produced by imipramine, desipramine, phenelzine or iprindole. To a large extent, the antagonism of antidepressant-induced reductions in 5-HT2-mediated behavior was coincident with the blockade of down-regulation of beta-adrenergic binding sites by both noradrenergic and serotonergic denervation. The functional interrelationship of 5-HT2 and beta-adrenergic receptors suggested by the present findings may provide insight into a common mechanism underlying the action of pharmacologically-distinct antidepressant drugs.

5,7-Dihydroxytryptamine↗

PubMed1988

Norepinephrine-stimulated inositol phospholipid breakdown in the rat cerebral cortex following serotoninergic lesion.

Norepinephrine (NE)-stimulated inositol phospholipid hydrolysis ("PI breakdown") in rat cerebral cortical miniprisms was used as a measure of alpha 1-adrenoceptor function following serotonin and/or NE depletion. The use of ascorbic acid to prevent autooxidation of the NE during the PI breakdown assay was found to be warranted. Treatment of rats with 5,7-dihydroxytryptamine and DSP4 produced selective depletions of serotonin (79-95%) and NE (69-85%), respectively, in cortical and hippocampal brain regions. The degree of cortical NE-stimulated PI breakdown in the lesioned animals was not significantly different from that in the control animals, suggesting that under the conditions used, serotonin and NE depletion do not lead to a changed sensitivity of alpha 1-adrenoceptors coupled to PI breakdown in the rat cortex.

5,7-Dihydroxytryptamine↗

PubMed1988

Intrathecal noradrenaline restores 5-methoxy-N,N-dimethyltryptamine induced antinociception abolished by intrathecal 6-hydroxydopamine.

Intrathecal administration of 6-hydroxydopamine (6-OHDA) abolished the antinociceptive effects of acute administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 1 mg/kg, s.c.) in the hot-plate, tail-flick and shock titration tests of nociception. The antinociceptive effects of 5-MeODMT, abolished by the prior intrathecal 6-OHDA treatment, were restored by intrathecal administration (2 or 1 microgram) of noradrenaline (NA), immediately prior to 5-MeODMT, in all three tests of nociception. Biochemical analysis confirmed severe NA depletions (95 percent loss) in the lumbar and thoracic regions of the spinal and much lesser dopamine depletions (25-35 percent loss). Intrathecal 5,7-dihydroxytryptamine (5,7-DHT) attenuated 5-MeODMT induced antinociception in the tail-flick test and combined NA + 5-MeODMT induced antinociception in the hot-plate and tail-flick tests. Intrathecal administration of 5,7-DHT caused a severe depletion of 5-hydroxytryptamine in the lumbar region of the spinal cord. The present findings demonstrate further the modulatory role of NA upon serotonergic systems in nociception and indicate the necessity of NA availability for induction of 5-MeODMT analgesia.

5,7-Dihydroxytryptamine↗