UNIPROT:P08908 - FACTA Search

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)

Using in situ hybridization techniques, the expression of 5-HT1A receptor mRNA was measured within the hippocampal formation after bilateral adrenalectomy (ADX). After 24 hr ADX, 5-HT1A receptor mRNA expression was significantly increased in all hippocampal subfields in ADX animals relative to sham-operated controls (SHAM). The magnitude of the increase was most pronounced within CA2 (127%) and CA3/4 (94%)-subfields of dorsal hippocampus, intermediate in the dentate gyrus (73%), and least within CA1 (60%). Administration of exogenous corticosterone (CORT) at the time of ADX maintained the level of 5-HT1A receptor mRNA expression within the range of SHAM animals. In vitro receptor autoradiographic analysis of 5-HT1A receptors in adjacent sections from the same animals indicated a simultaneous increase in 5-HT1A binding throughout the hippocampus in response to ADX. 5-HT1A binding increased to a similar extent (approximately 30%) in CA subfields and dentate gyrus but remained within SHAM levels in CORT-replaced animals. 5-HT1A receptor mRNA levels were also increased in hippocampal subregions of 1 week ADX animals relative to SHAM animals. Within both CA1 and CA2 subfields, the increments were approximately double those observed after 1 d ADX. 5-HT1A receptor binding was increased in every hippocampal subfield to a similar extent as that observed after 1 d ADX. Increases in both 5-HT1A receptor mRNA expression and 5-HT1A receptor binding were preventable by administration of exogenous CORT at the time of ADX. Hippocampal 5-HT1C receptor mRNA and D1 receptor mRNA expression were not significantly altered by either acute or chronic ADX treatment. These data indicate that adrenal steroids may selectively regulate hippocampal 5-HT1A receptors at the level of 5-HT1A receptor mRNA expression.
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PMID:Corticosteroids regulate brain hippocampal 5-HT1A receptor mRNA expression. 844 Oct 16

The injection of 1 microgram of pertussis toxin, which inactivates Gi/o proteins, in the rat dorsal raphe nearly abolished the responsiveness of serotonin (5-HT) neurons to microiontophoretic applications of 5-HT and selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) without altering their responsiveness to of gamma-aminobutyric acid (GABA). In contrast, the injection of 1 microgram of cholera toxin, which causes an activation of Gs proteins, did not alter the responsiveness of 5-HT neurons to 5-HT, 8-OH-DPAT or GABA. Such in situ injection of either toxin in the dorsal hippocampus decreased by about 90% the responsiveness of CA3 pyramidal neurons to microiontophoretic applications onto their cell body of 5-HT and 8-OH-DPAT, but not of GABA. The effectiveness of the stimulation of the ascending 5-HT pathway in suppressing the firing activity of the same neurons, which results from the release of 5-HT at the level of their dendritic tree, was also markedly decreased in the cholera toxin-treated rats, but intriguingly not in the pertussis toxin-treated rats. These results indicate that, on 5-HT neurons, the somato-dendritic 5-HT1A autoreceptor is coupled to Gi/o, but insensitive to the persistent activation of Gs proteins. In the CA3 region of the hippocampus, there would be two subsets of postsynaptic 5-HT1A receptors on the pyramidal neurons: those apposed to 5-HT terminals on their dendritic tree (denoted intrasynaptic) and those located on their cell body (denoted extrasynaptic). The former are cholera toxin sensitive, whereas the latter are sensitive to both pertussis and cholera toxins.
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PMID:Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: II. Effect of pertussis and cholera toxins. 847 3

The i.v. administration of the 5-hydroxytryptamine (5-HT)1A antagonist spiperone (1 mg/kg) antagonized the suppressant effect of microiontophoretic applications of 5-HT and of the selective 5-HT1A agonist 8-OH-DPAT on the firing activity of the rat dorsal raphe 5-HT neurons. In contrast, the same dose of spiperone did not alter the responsiveness to microiontophoretic applications of 5-HT and 8-OH-DPAT of pyramidal neurons in the CA3 region of the hippocampus, therefore indicating that spiperone does not act as a classical antagonist at these postsynaptic 5-HT1A receptors. After two daily injections of spiperone (5 mg/kg, i.p.) and a third one immediately before the experiment, the responsiveness of CA3 pyramidal neurons to 5-HT applied by microiontophoresis and to that released by the electrical stimulation of the ascending 5-HT pathway was markedly reduced. After 24, but not 12 or 48 h after a single injection of spiperone (5 mg/kg, i.p.), the responsiveness to exogenous and endogenous 5-HT was decreased. Smaller doses (1 and 2.5 mg/kg, i.p.) were ineffective. Haloperidol and ketanserin (5 mg/kg, i.p., 24 h before the experiment) were ineffective in blocking the responsiveness of CA3 pyramidal neurons to 5-HT, thereby demonstrating that the dopamine D2 and 5-HT2 properties of spiperone could not account for the attenuated responsiveness of the hippocampus neurons to 5-HT. Methiothepin (5 mg/kg, i.p., 24 h before recording), as for spiperone, antagonized the suppressant effect of 5-HT applied by microiontophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: I. Effect of spiperone. 847 32

Previous work in this laboratory demonstrated that in utero ethanol exposure is associated with abnormal development of the serotonergic system. Specific abnormalities included deficiencies of serotonin (5-HT) and its metabolites, and cortical 5-HT reuptake sites. The concentration of 5-HT1A receptors was also altered. The serotonin deficit was detected in the fetal ethanol-exposed brain, at an age when 5-HT would normally function as an essential trophic factor. Thus, it was hypothesized that the early 5-HT ethanol-associated deficit of an essential trophic factor (e.g. 5-HT) could contribute to subsequent developmental abnormalities in serotonergic neurons. In the present investigation we used quantitative autoradiography (QAR) to more fully characterize the developmental abnormalities in 5-HT reuptake sites in developing offspring of ethanol-fed rats. In addition, we attempted to overcome the potential negative impact of the ethanol-associated deficit of fetal 5-HT, by administering a 5-HT1A agonist, buspirone, to pregnant rats. These investigations demonstrated that postnatal (PN) 19 and/or 35 day ethanol-exposed offspring had a significant decrease in [3H]citalopram binding to 5-HT reuptake sites in the frontal cortex, parietal cortex, lateral hypothalamus, substantia nigra, medial septum, and striatum. In contrast, [3H]citalopram binding was increased in the dorsal raphe on PN5 and in the median raphe on PN19. No significant ethanol-associated changes were detected in the hippocampus CA3 region or in the amygdala. When [3H]citalopram binding was compared in the offspring of saline- and buspirone-treated dams, it appeared that maternal treatment with buspirone prevented or reversed most of the ethanol-associated developmental abnormalities in 5-HT reuptake sites. Buspirone prevented the decline in binding of [3H]citalopram in the frontal cortex, lateral hypothalamus, substantia nigra and medial septum. Similarly, buspirone treatment prevented the ethanol-associated increase in binding in the dorsal and median raphe. Additional experiments are needed to elucidate the impact of maternal buspirone treatment on the development of other neurotransmitter systems in offspring.
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PMID:Protective effects of maternal buspirone treatment on serotonin reuptake sites in ethanol-exposed offspring. 873 26

Serotonin (5-HT) projections from the ascending raphe nuclei reach the dorsal hippocampus via the cingulum bundle (CB) and fimbria-fornix (FF). Microinjection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the CB and FF produces a significant decrease in the density of 5-HT immunoreactive fibers in the hippocampus as early as 3 days postlesion (Zhou, F.C. and Azmitia, E.C. (1983) Brain Res. Bull., 373, 337-348). In the present study we used an anti-peptide antibody against the second extracellular loop of the 5-HT1A receptor and employed immunocytochemistry to examine changes in the expression and distribution of the 5-HT1A receptor in the hippocampus 14 days following administration of 5,7-DHT into the CB and FF. The density of 5-HT immunoreactive fibers was greatly reduced 14 days following the lesions. 5-HT1A immunoreactivity (IR) was localized to the proximal axon near the axon hillock of cells in the pyramidal cell layer of the cornu Ammonus and in the granule cell layer of the dentate gyrus. The intensity of 5-HT1A-IR was increased in the CA1 and dentate gyrus following 5,7-DHT lesions. Intensity in the CA3 also increased but not to a significant level. These findings demonstrate that 5-HT denervation in the hippocampus is followed by increased expression of the 5-HT1A receptor protein. These changes in receptor expression 14 days postlesion may represent adaptive changes by postsynaptic cells following reduced 5-HT innervation and may be the molecular basis for 5-HT1A receptor supersensitivity.
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PMID:Increased 5-HT1A receptor immunoreactivity in the rat hippocampus following 5,7-dihydroxytryptamine lesions in the cingulum bundle and fimbria-fornix. 878 27

The distribution of messenger ribonucleic acids (mRNA) for serotonin (5-HT) receptors of 1A, 2A and 1D alpha type (5-HT1A, 5-HT2A, and 5-HT1D alpha) was examined and compared in autoptic human brain by means of in-situ hybridization using cRNA probes, in those areas with the highest density of the receptors, as observed with binding techniques. The results showed that the 5-HT1A receptor mRNA was abundantly expressed in the layers II-VI of all cortical areas under examination, but the highest expression was found in the hippocampus, particularly in the granular cells of the dentate gyrus and in the pyramidal cell layer of the Hammon's horn. The 5-HT2A receptor mRNA was mainly present in the layers III-V of the cortex, with regional differences which were particularly marked in the striate area where the layer IV was specifically labeled. On the other hand, in the hippocampus, 5-HT2A receptor mRNA was restricted to the pyramidal cell layer of the CA1 field of the Hammon's horn. No expression of both 5-HT2A and 5-HT1D alpha receptors was detected in the caudate nucleus and in putamen where only a light labeling by means of the 5-HT1A receptor probe was detected. The 5-HT1D alpha receptor mRNA was found only in the CA3 field of the Hammon's horn. These findings confirm that 5-HT receptors are widely distributed in the brain, but that the different subtypes possess a selective localization in different neuronal populations which, in turn, may express one or more receptors. The regional differences may represent the anatomical substrate of different serotonergic functions and dysfunctions.
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PMID:Comparative anatomical distribution of serotonin 1A, 1D alpha and 2A receptor mRNAs in human brain postmortem. 880 30

In this study, the 5-HT1A agonistic activity of R- and S-enantiomers of the prototypical 5-HT1A agonist 8-OH-DPAT was investigated using in vivo microiontophoresis and the hypothermic response in rats. Both the R- and S-enantiomers suppressed current-dependently the firing activity of dorsal hippocampus CA3 pyramidal neurons. The number of spikes suppressed/nA of R-(+)-OH-DPAT was about 2-fold greater than that of S-(-)-OH-DPAT, which indicates greater agonistic activity of the R-enantiomer. The determination of the effectiveness of 5-HT in suppressing the firing activity of CA3 pyramidal neurons prior to and during application of either the R- or S-enantiomer showed that both compounds antagonized the effect of 5-HT, thus demonstrating their partial agonistic activity. Racemic 8-OH-DPAT produced a dose-dependent hypothermia which was attenuated by the 5-HT1A antagonist pindolol, but not by the nonselective 5-HT antagonist methysergide. Similarly, both R- and S-enantiomers induced a dose-dependent hypothermia, which was greater and longer lasting in the case of R-(+)-OH-DPAT when compared to S-(-)-OH-DPAT. In conclusion, R-(+)-OH-DPAT, displayed a greater agonistic activity at 5-HT1A receptors than S-(-)-OH-DPAT, both in suppressing firing activity of CA3 pyramidal neurons and in decreasing body temperature. Nevertheless, both compounds behaved as partial agonists.
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PMID:Partial agonistic activity of R- and S-enantiomers of 8-OH-DPAT at 5-HT1A receptors. 882 Jan 75

In microdialysis studies, somatodendritic 5-HT1A receptors in the dorsal raphe nucleus (DRN) were activated by the local infusion of 50 microM citalopram, a selective 5-HT reuptake inhibitor (SSRI). This reduced extracellular 5-HT by about 50% in dorsal striatum, an area receiving 5-HT afferents exclusively from the DRN. (-)Pindolol dose-dependently attenuated this citalopram-induced reduction of striatal extracellular 5-HT. Consistent with its 5-HT reuptake blocking properties, single doses of the SSRI paroxetine (1 and 3 mg/kg IP) and citalopram (1 mg/kg IP) significantly elevated extracellular 5-HT in the dorsal striatum. Pretreatment with (-)pindolol (15 mg/kg IP) potentiated the effect of 3 mg/kg paroxetine and 1 mg/kg citalopram on striatal extracellular 5-HT. A 2-day treatment with 10 mg/kg/day (SC) of paroxetine reduced by 60% the spontaneous activity of 5-HT neurons of the DRN. However, 5-HT neurons displayed normal activity in rats treated with paroxetine and (-)pindolol for 2 days. The inhibitory effect of LSD on 5-HT neuronal firing activity was also markedly attenuated in (-)pindolol-treated rats, indicating that somatodendritic 5-HT1A receptors were blocked by (-)pindolol. To determine whether (-)pindolol also blocked postsynaptic 5-HT1A receptors in hippocampus, 5-HT and the prototypical 5-HT1A agonist 8-OH-DPAT were applied by microiontophoresis onto CA3 pyramidal neurons following the same treatment. (-)Pindolol did not modify the responsiveness of these neurons to 5-HT and 8-OH-DPAT. Taken together, these results indicate that (-)pindolol can potentiate the effects of an SSRI on extracellular 5-HT concentration by preventing the activation of somatodendritic 5-HT1A autoreceptors resulting from the blockade of the 5-HT transporter in the raphe. This presumably leads to enhanced 5-HT neurotransmission because (-)pindolol would not alter the responsiveness of certain postsynaptic 5-HT1A receptors, such as those located on hippocampal CA3 pyramidal neurons. These results provide a neurobiological basis for the reported potentiation of certain antidepressant drugs by pindolol in major depression.
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PMID:Effect of pindolol on the function of pre- and postsynaptic 5-HT1A receptors: in vivo microdialysis and electrophysiological studies in the rat brain. 888 89

Serotonergic (5-hydroxytryptamine; 5-HT) neurotransmission has been implicated in the regulation of cognitive function and this neurotransmitter system may underlie selective neuronal degeneration found in the aging hippocampus. Age-dependent changes in 5-HT function of hippocampal CA3 subfield pyramidal neurons were evaluated in female Fischer 344 rats (2 and 17 months) following denervation of the serotonergic afferents to the dorsal hippocampus using the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). Vehicle (ascorbic saline) or 5,7-DHT was administered bilaterally in the fimbria-fornix/cingulum bundle and dorsal pyramidal cell responses to microiontophoretic application of 5-HT, the 5-HT1A agonist (+/-)-8-hydroxy-2-(di-N-propylamino) tetralin, the 5-HT1A antagonist WAY 100,135 and N-methyl-D-aspartate were recorded at 3 weeks post-lesion. Independent of changes in sensitivity to the inhibitory effects of 5-HT with aging, the time to recovery of cell firing following application of 5-HT was significantly increased in the 18 months 5,7-DHT group compared to the 18 month Vehicle and 3 month 5,7-DHT groups (3.3- and 2.6-fold, respectively). These results demonstrate that serotonergic neurotransmission is altered with aging following a selective neurotoxic insult to the hippocampus.
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PMID:Serotonergic function of aging hippocampal CA3 pyramidal neurons: electrophysiological assessment following administration of 5,7-dihydroxytryptamine in the fimbria-fornix and cingulum bundle. 898 Dec 38

Fluoxetine is a 5-hydroxytryptamine (5-HT, serotonin)-selective reuptake inhibitor (SSRI) and is one of the main drugs used for the treatment of depression. Because it takes 2 to 3 weeks of treatment before clinical efficacy is manifest, the acute actions of fluoxetine cannot account for the clinical actions of the drug. The chronic effects of fluoxetine have not been completely delineated. The experiments detailed here investigate the chronic effects of fluoxetine on 5-HT and gamma-aminobutyric acid (GABA) receptor-mediated actions using intracellular recording techniques in hippocampal brain slices. Rats were treated with fluoxetine for 3 weeks via osmotic minipumps implanted s.c. Fluoxetine and norfluoxetine plasma levels were determined. The hippocampal pyramidal cell characteristics and the 5-HT1A and GABA(B) receptor-mediated hyperpolarization were measured in the CA1 and the CA3 subfields. The 5-HT4 receptor-mediated decrease in the slow afterhyperpolarization amplitude was also recorded in area CA1. The time constant, magnitude of the change in resistance during 300-ms hyperpolarizing current pulses and half-decay time of the sAHP were altered by chronic fluoxetine treatment in area CA1 pyramidal cells. No changes were seen in any of the active or passive membrane properties of the CA3 hippocampal pyramidal cells. Fluoxetine treatment increased the potency of 5-HT for the 5-HT1A receptor-mediated hyperpolarization in area CA1, but not area CA3, and decreased the potency of baclofen for the GABA(B) receptor-mediated hyperpolarization in area CA1, but not area CA3. The characteristics of the concentration-response curve for the 5-HT-mediated decrease in sAHP amplitude in area CA1 were not altered by fluoxetine treatment. Chronic fluoxetine selectively and differentially altered the cell characteristics and the 5-HT1A and GABA(B) receptor-mediated responses in area CA1 of the hippocampus, which forms the final common output of the hippocampus.
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PMID:Fluoxetine selectively alters 5-hydroxytryptamine1A and gamma-aminobutyric acidB receptor-mediated hyperpolarization in area CA1, but not area CA3, hippocampal pyramidal cells. 910 87

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