Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoradiographic and membrane binding studies with [3H](R,S)- or [3H](S)-zacopride were performed in combination with lesions using various neurotoxins in an attempt to identify which neuronal cell types are endowed with 5-HT3 receptors in the rat central nervous system. Lesions of noradrenergic (by DSP-4), dopaminergic (by 6-hydroxydopamine) and serotonergic (by 5,7-dihydroxytryptamine) systems had little effect generally on the density of 5-HT3 receptors labelled with [3H](R,S)- or [3H](S)-zacopride in various regions of the brain and the spinal cord. The only exception was the amygdala where a significant loss (approximately -20%) of 5-HT3 receptors labelled by [3H](R,S)-zacopride was associated with the selective lesion of serotonergic fibres by 5,7-dihydroxytryptamine. Microinjection of kainic or ibotenic acid into the dorsal and ventral hippocampus reduced the density of 5-HT1A receptors labelled with [3H]8-OH-DPAT (approximately -45%) as expected from their known location on intrinsic neuronal cell bodies and/or dendrites. In contrast, the same lesion did not affect 5-HT3 receptors, suggesting their location on fibres 'en passage'. At the spinal level, 5-HT3 receptors were found to exist on primary afferent fibres terminating within the superficial layers of the dorsal horn, as shown by the marked reduction in the local autoradiographic labelling by [3H](S)-zacopride after either dorsal rhizotomy (-81%) or neonatal capsaicin treatment (-72%). These data suggest that 5-HT3 receptors in the central nervous system are generally located presynaptically on nerve terminals or fibres of non-monoaminergic neurones.
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PMID:5-HT3 receptors in the rat central nervous system are mainly located on nerve fibres and terminals. 833 Feb 6

1. The 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) has been evaluated in a mouse model for detecting potential antidepressants (Porsolt test). The effects of various receptor antagonists, lesions of brain monoaminergic neurones and chronic drug treatments on this 8-OH-DPAT-induced response have also been determined. 2. 8-OH-DPAT (0.3-10.0 mg kg-1, s.c.) dose-dependently increased the mobility of mice in the Porsolt test. Other selective 5-HT1A receptor ligands (0.3-30 mg kg-1, s.c.) either mimicked the 8-OH-DPAT response (ipsapirone, at 10 and 30 mg kg-1, s.c.) or were inactive (buspirone and gepirone). However, each of these compounds (< or = 100 mg kg-1, p.o.) inhibited the response to 8-OH-DPAT (3 mg kg-1, s.c.) when given concurrently. 3. The putative 5-HT1A antagonists, spiroxatrine (1-30 mg kg-1, p.o.), (+/-)-pindolol (30 mg kg-1, p.o.) and methiothepin (3-10 mg kg-1, p.o.), each attenuated the 8-OH-DPAT (3 mg kg-1, s.c.)-induced increase in mobility. 4. The dopamine D1 receptor antagonist, SCH 23390 (3-10 mg kg-1, p.o.), weakly reversed the 8-OH-DPAT response. Antagonists at 5-HTlc/5-HT2 receptors (ketanserin; 0.1-3.0 mg kg-1, p.o.),5-HT3 receptors (ondansetron; 0.03-10mg kg-1, p.o.), at-adrenoceptors (prazosin; 1-3mgkg-1, p.o.),alpha2 -adrenoceptors (idazoxan; 3-30mg kg-1, p.o.), alpha 1-adrenoceptors (metoprolol; 1-30mgkg-1, p.o.),beta 2-adrenoceptors (ICI 118,551; 1-30 mg kg-1, p.o.), dopamine D2 receptors (sulpiride; 10-300mg kg-',p.o.) and opiate receptors (naloxone; 3-100 mg kg-', p.o.) had no effect on the 8-OH-DPAT response.5. Selective destruction of 5-HT neurones with 5,7-dihydroxytryptamine or inhibition of 5-HT synthesis with p-chlorophenylalanine did not change the 8-OH-DPAT response in the Porsolt test. This response was also unaltered by pretreatment with the noradrenergic neurotoxin, DSP-4.6. Administration of 8-OH-DPAT (3 mg kg-1, s.c.) twice-daily for 10 days attenuated the hypothermia,but not the increased mobility, induced by 8-OH-DPAT (3 mg kg-1, s.c.). Similarly, repeated administration of amitriptyline (3-30 mg kg-1), desipramine (3-30 mg kg-1) or dothiepin (10-100 mg kg-1) also attenuated the former, but not the latter, response.7. We conclude that 8-OH-DPAT produces an antidepressant-like effect in the Porsolt test which is mediated via postsynaptic 5-HT1A receptors.
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PMID:Mediation of the antidepressant-like effect of 8-OH-DPAT in mice by postsynaptic 5-HT1A receptors. 846 55

Autoradiographic studies were performed in combination with dorsal rhizotomy or selective lesion of descending serotonergic or noradrenergic systems in an attempt to identify the neuronal cell types endowed with the serotonin 5-HT1A, 5-HT1B and 5-HT3 receptors in the rat spinal cord. Unilateral sectioning of seven dorsal roots (C4-T2) at the cervical level produced a marked decrease (approximately-75%, 10 days after the surgery) in the binding of [125I]iodozacopride to 5-HT3 receptors in the superficial layers of the ipsilateral dorsal horn, further confirming the preferential location of these receptors on primary afferent fibres. In addition, a significant decrease (approximately 20%) in the binding of [3H]8-OH-DPAT to 5-HT1A receptors and of [125I]GTI to 5-HT1B receptors was also observed in the same spinal area in rhizotomized rats, suggesting that a small proportion of these receptors are also located on primary afferent fibres. The labelling of 5-HT1B receptors was significantly decreased (-12%) in the dorsal horn at the cervical (but not the lumbar) level, and that of 5-HT3 receptors was unchanged in the whole spinal cord in rats whose descending serotonergic projections had been destroyed by 5,7-dihydroxytryptamine. Conversely, the labelling of 5-HT1A receptors was significantly increased in the cervical (+13%) and lumbar (+42%) dorsal horn in 5,7-dihydroxytryptamine-lesioned rats. Similarly, [3H]8-OH-DPAT binding to 5-HT1A receptors significantly increased (+26%) in the lumbar (but not the cervical) dorsal horn in rats whose noradrenergic systems had been lesioned by DSP-4. The labelling of 5-HT1B receptors was also increased (+31% at the cervical level; +17% at the lumbar level), whereas that of 5-HT3 receptors remained unchanged in these animals. These data indicate that complex adaptive changes in the expression of 5-HT1A and 5-HT1B receptors occurred in the rat spinal cord following the lesion of descending monoaminergic systems.
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PMID:Effects of dorsal rhizotomy and selective lesion of serotonergic and noradrenergic systems on 5-HT1A, 5-HT1B, and 5-HT3 receptors in the rat spinal cord. 874 67

8-Hydroxy(di-n-propylamino)tetralin (8-OH-DPAT; 0.1-50 mg/kg i.p.) evoked a dose-dependent mydriatic response in conscious mice (ED50 = 5.8 mg/kg i.p.) which was maximal after 10 min. 8-OH-DPAT (2 mg/kg i.p.)-induced mydriasis was attenuated by the alpha 2-adrenoceptor antagonists, idazoxan (1 and 3 mg/kg i.p.) and yohimbine (1 and 3 mg/kg i.p.), by the 5-HT1 receptor antagonists, pindolol (10 mg/kg i.p.) and quipazine (2 mg/kg i.p.), and by the selective 5-HT1A receptor antagonist, (-)-N-tert-butyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenyl propionamide ((-)-WAY 100135; 1-10 mg/kg s.c.). These data argue that both central alpha 2-adrenoceptors and 5-HT1A receptors are involved in the mediation of mydriasis induced by 8-OH-DPAT. The synaptic location of these receptors was determined using either N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 100 mg/kg i.p.) or 5,7-dihydroxytryptamine (5,7-DHT; 75 micrograms i.c.v.)+p-chlorophenylalanine (PCPA; 200 mg/kg i.p.); these lesioning procedures respectively produced highly significant losses of whole brain noradrenaline (72% depletion) and 5-HT (78% depletion). The former abolished 8-OH-DPAT (5 mg/kg i.p. (ED50)) mydriasis, whereas the latter was without effect. 8-OH-DPAT (0.5-5 mg/kg i.p.) also dose-dependently increased the noradrenaline metabolite, 3-methoxy-4-hydroxy-phenylglycol (MHPG), in mouse whole brain minus cerebellum. Taken together these results show that 8-OH-DPAT initially stimulates 5-HT1A receptors, and it is likely that this is followed by release of noradrenaline onto postsynaptic alpha 2-adrenoceptors, the latter effect being responsible for the mydriatic response.
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PMID:8-OH-DPAT-induced mydriasis in mice: a pharmacological characterisation. 898 15

The present study sought to verify effects of 5-HT on synaptic density at the ultrastructural level, to determine whether the 5-HT1a receptor is important for the maintenance of synaptic connections and to obtain evidence implicating S100 beta in the apparent neurotrophic actions of 5-HT. Reduction of hippocampal 5-HT with para-chloroamphetamine (PCA) resulted in a significant decline in the synaptic density of the dentate molecular layer. Reduction of norepinephrine with DSP-4 produced a slight decrease in the number of molecular layer synapses, but this difference was not statistically different from control values. 5-HT1a antagonist treatment resulted in a decline in synaptic density comparable to that observed following PCA treatment. These observations suggest that 5-HT functions to maintain synaptic connections in the dentate molecular layer via a 5-HT1a mechanism. To determine whether the change in synaptic density was due to the action of 5-HT on neuronal receptors or astrocytic receptors, a monoclonal antibody against S100 beta was infused into the lateral ventricle for seven days. Controls received infusions of normal goat serum. Half of the rats from the anti-S100 beta and control groups also received daily injections of NAN-190. Anti-S100 beta infusion resulted in a significant (p < 0.01) decrease in synapses compared to serum controls. Concomitant NAN-190 administration did not enhance synapse loss in the anti-S100 beta group. The results of this study suggest that the maintenance of synaptic connections in the dentate molecular layer is influenced by S100 beta levels that are controlled by 5-HT stimulation of astrocytic 5-HT1a receptors.
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PMID:Serotonin regulates synaptic connections in the dentate molecular layer of adult rats via 5-HT1a receptors: evidence for a glial mechanism. 951 68

The effects of selective manipulations of activity of the serotonergic and noradrenergic systems were examined in the rat model of visceral pain. It was found that neither p-chlorophenylalanine(p-CPA)- nor N-chloro-ethyl-2,2--bromo-benzylamine(DSP-4)-induced strong and selective depletion of the brain and spinal cord serotonin and noradrenaline, respectively, changed in a significant way rat visceral pain perception. On the other hand, 8-OH-DPAT, a full selective 5-HT1A receptor agonist, prazosin, an alpha1-adrenoceptor antagonist, clonidine, an alpha2-adrenoceptor agonist, and two beta-adrenoceptor antagonists: propranolol and metoprolol, dose-dependently reduced the number of body writhes induced by intraperitoneally administered 2% solution of acetic acid (the writhing test). The results obtained with selective receptor ligands, DSP-4 and p-CPA, indicate that the noradrenergic and serotonergic innervation of the central nervous system contribute in a complex way to the animal behavior in the writhing test. The 5-HT1A receptors and alpha2-adrenoceptors play an inhibitory role in the expression of rat behavior in this model of visceral pain. On the other hand, adrenergic alpha1 and beta1 receptors facilitate the behavioral effects of the irritant agent.
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PMID:Role of serotonergic and noradrenergic systems in a model of visceral pain. 1199 65

The aim of this study was to assess the 5-HT1A receptor reactivity after neonatal noradrenergic neurons' lesion. DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), 50 mg/kg, was administered 30 min after a selective serotonin reuptake inhibitor (SSRI)--zimelidine (10 mg/kg) on the 1st and 3rd day of life. Zimelidine was used to prevent serotonin (5-HT) depletion. 5-HT1A autoreceptor is involved in the regulation of 5-HT release as well as the pathogenesis of depression. During a microdialysis study of anaesthetized rats, the 5-HT1A receptor agonist, R-(+)-8-OH-DPAT (0.1 mg/kg), decreased 5-HT release in the medial prefrontal cortex of control rats but this effect was significantly attenuated in DSP-4-treated animals (10-12 weeks old). To further determine which type of receptor, either pre or postsynaptically located, is involved in the attenuated response to the 5-HT1A receptor agonist in lesioned rats, behavioral tests were conducted. In the forced swimming test, DSP-4 treated rats after saline injection, displayed shorter immobility time in comparison to control rats. R-(+)-8-OH-DPAT (0.5 mg/kg) evoked an antidepressant-like effect in control and DSP-4 treated rats in a learned helplessness paradigm as well as the forced swimming test. The results of this study provided further support for the exclusive desensitization of 5-HT1A autoreceptor in adult rats with neonatal lesion of the central noradrenergic system.
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PMID:Reactivity of 5-HT1A receptor in adult rats after neonatal noradrenergic neurons' lesion--implications for antidepressant-like action. 1878 11

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a highly selective neurotoxin for noradrenergic projections originating from the locus coeruleus (LC). The outcome of the systemic DSP-4 treatment of newborn rats is an alteration in postnatal development of the noradrenergic system, involving the permanent denervation of distal noradrenergic projection areas (neocortex, hippocampus, spinal cord), accompanied by noradrenergic hyperinnervation in regions proximal to the LC cell bodies (cerebellum, pons-medulla). DSP-4 is well tolerated by developing rats and does not increase the mortality rate. Permanent noradrenergic denervation in the cerebral cortex and spinal cord is present at all developmental stages, although this effect is more pronounced in rats treated with DSP-4 at an early age, i.e., up to postnatal day 5 (PND 5). Notably, regional hyperinnervation is a hallmark of neonatal DSP-4 treatment, which is not observed after either prenatal or adult DSP-4 application. In contrast to robust biochemical changes in the brain, DSP-4 treatment of newborn rats has a marginal effect on arousal and cognition functions assessed in adulthood, and these processes are critically influenced by the action of the noradrenergic neurotransmitter, norepinephrine (NE). Conversely, neonatal DSP-4 does not significantly affect 5-hydroxytryptamine (serotonin; 5-HT), dopamine (DA), gamma-aminobutyric acid (GABA), and histamine levels in brain. However, as a consequence of altering the functional efficacy of 5-HT1A, 5-HT1B, DA, and GABA receptors, these neurotransmitter systems are profoundly affected in adulthood. Thus, the noradrenergic lesion obtained with neonatal DSP-4 treatment represents a unique neurobiological technique for exploring the interplay between various neuronal phenotypes and examining the pathomechanism of neurodevelopmental disorders.
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PMID:Selective Lifelong Destruction of Brain Monoaminergic Nerves Through Perinatal DSP-4 Treatment. 2642 51