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)

Male rats housed in mixed-sex groups quickly established dominance hierarchies in which subordinates appeared severely stressed. Subordinate rats had elevated basal corticosterone (CORT) levels relative to dominants and individually housed controls. Several subordinates had blunted CORT responses to a novel stressor, leading to the classification of subordinates as either stress-responsive or nonresponsive. Binding to 5-HT1A receptors was reduced in stress-responsive subordinates compared to controls throughout hippocampus and dentate gyrus. Decreased binding was observed in nonresponsive subordinates only in CA3 of hippocampus. In addition, 5-HT1A binding was decreased in CA1, CA3, and CA4 in dominants compared to controls. Binding to 5-HT2 receptors was increased in parietal cortex in both responsive and nonresponsive subordinates compared to controls. No changes were observed in binding to 5-HT1B receptors. These results are discussed in the context of regulation of the serotonergic system by stress and glucocorticoids and possible relevance to the pathophysiology of depression.
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PMID:Serotonin receptor binding in a colony model of chronic social stress. 777 47

The densities of serotonin1A (5-HT1A) receptors, labeled with [3H]8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), were examined in the CNS of alcohol-naive adult male alcohol-preferring (P) and -nonpreferring (NP) rats using quantitative autoradiography. The densities of sites labeled with 2 nM [3H]8-OH-DPAT were a) 20-30% higher in the medial prefrontal, frontal (layers 1, 2, and layers 3-6), parietal (layers 3-6), and cingulate cortex; b) 35-40% higher in the retrosplenial, occipital (all layers), temporal (all layers) cortex; and c) 15% higher in the entorhinal cortex of the P compared with the NP rat. Within the hippocampus, significant differences between the rat lines were observed only in the posterior portion where the densities of [3H]8-OH-DPAT labeled sites were a) 10-15% higher in the dorsal dentate gyrus, dorsal CA1, and dorsal CA3 regions; and b) 15-25% higher in the anterior ventral hippocampal area and ventral dentate gyrus of the P relative to the NP line. In contrast to the above results, the densities of [3H]8-OH-DPAT labeled sites were 15-20% lower in the dorsal, paradorsal, and median raphe nuclei of the P compared with the NP rat. No differences in [3H]8-OH-DPAT binding between the rat lines were found in several basal ganglia, limbic, and brain stem regions. The data indicate that there are greater numbers of postsynaptic 5-HT1A receptors in certain parts of the cerebral cortex and hippocampus of the P compared with the NP rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional serotonin1A receptors in the CNS of alcohol-preferring and -nonpreferring rats. 781 92

1. Voltage- and current-clamp intracellular recordings were performed on rat CA3 hippocampal pyramidal cells in a slice preparation. 2. Under current-clamp conditions, 5-hydroxytryptamine (5-HT) or baclofen (BAC) perfusion hyperpolarized CA3 cells. 3. Under single-electrode voltage-clamp conditions, 5-HT perfusion elicited an outward current flow that was blocked by 2 mM BaCl2 but not by 100 microM CdCl2. 4. The Emax of the current response in CA3 was larger than that elicited in CA1 and the potency was less in CA3 than CA1. 5. Increasing the external potassium concentration shifted the reversal potential for the 5-HT-mediated response. 6. The potassium current exhibited inward rectification. 7. The BAC- and 5-HT-mediated currents were not additive. 8. Pertussis-toxin (PTX) treatment blocked both 5-HT- and BAC-elicited hyperpolarizations. 9. On the basis of these results, we conclude that 5-HT hyperpolarized hippocampal CA3 pyramidal cells by increasing an inward-rectifying potassium conductance. Furthermore both the 5-HT1A and gamma-aminobutyric acidB (GABAB) receptors are linked to potassium channels via a PTX-sensitive G protein.
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PMID:5-HT1A receptor linked to inward-rectifying potassium current in hippocampal CA3 pyramidal cells. 793 9

The present study was undertaken to investigate the nature of the effect of pertussis toxin on the responsiveness of two potentially distinct subgroups of postsynaptic serotonin1A (5-HT1A) receptors of rat hippocampus CA3 pyramidal neurons: those located at the level of the cell body, which can be activated by microiontophoretically-applied 5-HT1A receptor agonists, and those located on dendrites, which can be activated by endogenous serotonin released by the stimulation of the ascending serotoninergic pathway. The former receptors (denoted as extrasynaptic) have been previously demonstrated to be sensitive to pertussis toxin, whereas the latter (denoted as intrasynaptic) have been shown to be pertussis toxin-insensitive. Rats treated with the 5-HT1A receptor agonists flesinoxan or BMY 42568 were used to determine whether tonic activation of extrasynaptic 5-HT1A receptors would prevent their inactivation by pertussis toxin. A pretreatment with p-chlorophenylalanine was used to determine whether a serotonin depletion would render the intrasynaptic 5-HT1A receptors sensitive to pertussis toxin. The responsiveness of CA3 pyramidal neurons to the suppressant effects of microiontophoretically-applied serotonin, 8-hydroxy-2-(di-n-propylamin)-tetralin, baclofen and GABA or to endogenously-released serotonin, elicited by the stimulation of the ascending serotoninergic pathway, was studied one to 10 days after the intrahippocampal injection of pertussis toxin. When compared to control saline-treated rats, the treatments with flesinoxan (5 mg/kg/day, s.c.) and BMY 42568 (5 mg/kg/day, s.c.) delivered for 14 days by osmotic minipumps, starting three days prior to the injection of pertussis toxin, significantly attenuated the effect of pertussis toxin on the responsiveness of CA3 pyramidal neurons to microiontophoretic applications of serotonin and 8-hydroxy-2-(di-n-propylamino)-tetralin, as well as baclofen, an agonist of GABAB receptors, which share the same G proteins with 5-HT1A receptors. The two-day pretreatment with p-chlorophenylalanine (350 mg/kg/day, i.p.) did not render the intrasynaptic 5-HT1A receptors sensitive to pertussis toxin, as indicated by the unchanged efficacy of the stimulation of the ascending serotonin pathway in the suppressing the firing activity of CA3 dorsal hippocampus pyramidal neurons. Our results suggest that the sustained activation of extrasynaptic 5-HT1A receptors prevents the pertussis toxin-induced ADP ribosylation of G protein alpha subunit, and thereby protects an amount of G proteins sufficient to maintain the function, not only of 5-HT1A, but also of GABAB receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Agonist occupation of serotonin1A receptors in the rat hippocampus prevents their inactivation by pertussis toxin. 796 92

Prenatally protein malnourished rats born to dams maintained on a 6% casein diet during pregnancy and then fostered at birth to females on a 25% casein diet show adult alterations in hippocampal kindling and long-term potentiation and behavioral changes that all suggest dysfunction of hippocampal formation (HF). In the present investigation, compared to well-nourished controls, 220 day malnourished rats exhibited a decrease in the 5-HT fiber density in the dentate gyrus (DG) and CA3 subfield and, a 15-25% decrease 5-HT uptake sites assayed with [3H]-citalopram in CA3 and CA1. In malnourished rats, 5-HT1A receptors assayed with [3H]8-OH-DPAT were decreased by 20% in CA3. Because most hippocampal subfields showed no 5-HT changes, hippocampal 5-HT levels determined via HPLC methods were similar in adult malnourished and control rats. These results suggest that there are localized changes in the 5-HT afferent system in the hippocampal formation of the 220 day prenatally protein malnourished rat. Considering the 5-HT afferent input to inhibitory intrahippocampal neurons, the decreased 5-HT plexus may result in increased inhibition within specific hippocampal subfields despite overall normal levels of 5-HT in the total HF.
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PMID:Prenatal protein malnutrition effects on the serotonergic system in the hippocampal formation: an immunocytochemical, ligand binding, and neurochemical study. 808 44

It has been suggested that postsynaptic 5-HT1A receptors in the hippocampus, innervated by 5-HT neurons localized in the median raphe nucleus, mediate adaptive or coping responses to aversive events and that dysfunction of this system is related to symptoms of depression. To test this hypothesis we investigated the expression of c-fos mRNA in animals submitted to immobilization stress. The results showed that c-fos mRNA expression is significantly increased in the dentate gyrus and CA1-CA3 regions of the hippocampus after 30 min of forced restraint, suggesting that this structure is activated during stress. To investigate the role of 5-HT neurotransmission in the hippocampus on adaptation to aversive events we immobilized rats for 2 h and tested them 24 h later in an elevated plus-maze. Our results showed that the previous restraint period decreases exploration of open arms in the maze. This effect was reversed by bilateral microinjection of zimelidine (20 and 100 nmol), a 5-HT re-uptake blocker, or 8-OH-DPAT (3 nmol), a 5-HT1A agonist, into the dorsal hippocampus immediately after restraint. These results are compatible with the idea that postsynaptic 5-HT1A receptors located in the hippocampus participate in the development of tolerance to aversive events.
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PMID:Hippocampal 5-HT receptors and consolidation of stressful memories. 813 41

Quantitative receptor autoradiography was used to examine the 5-hydroxytryptamine (5-HT, serotonin) binding sites labelled with serotonin-5-O-carboxymethyl-glycyl-[125I]tyrosinamide ([125I]GTI) in human and guinea-pig brain. Competition experiments using 5-carboxamidotryptamine (5-CT), 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP 93129) and sumatriptan revealed monophasic displacement curves in various brain regions, suggesting that a homogeneous population of 5-HT1D binding sites was labelled. Displacement of [3H]5-HT (in the presence of 100 nM 8-hydroxy-2(N-dipropylamino)tetralin (8-OH-DPAT) and 100 nM mesulergine) with unlabelled GTI resulted in monophasic competition curves in substantia nigra, globus pallidus and central gray. In contrast, biphasic displacement was observed in hippocampus, nucleus accumbens, claustrum, caudate-putamen and frontal cortex. The distribution of [125I]GTI sites was compared to that of [3H]5-HT binding sites (under so-called '5-HT1D conditions', i.e. in the presence of 100 nM 8-OH-DPAT and 100 nM mesulergine, in order to block 5-HT1A and 5-HT1C sites, respectively) in human and guinea-pig brain. Qualitative analysis revealed differences in the distributions of [125I]GTI and [3H]5-HT binding sites. Regions such as CA3 and CA4 of the hippocampus, claustrum and putamen showed [3H]5-HT binding (under '5-HT1D conditions') but no [125I]GTI binding sites, indicating that [3H]5-HT labels besides a GTI sensitive (5-HT1D) receptor population, a non-5-HT1A/1B/1C/1D [3H]5-HT binding site in human and guinea-pig brain. The distribution of these non-5-HT1A/1B/1C/1D [3H]5-HT binding sites was studied with [3H]5-HT under conditions where 5-HT1A, 5-HT1C and 5-HT1D [3H]5-HT binding sites were saturated by the presence of 100 nM 8-OH-DPAT, 100 nM mesulergine and 1 microM GTI. Significant densities of these non-5-HT1A/1B/1C/1D sites were observed in cortical areas, hippocampal structures, nucleus accumbens, amygdala, caudate-putamen and claustrum. It is concluded that [125I]GTI does not label the 5-HT1E binding site, since all competition curves obtained with this radioligand were monophasic. By contrast, [3H]5-HT labels non-5-HT1A/1B/1C/1D [3H]5-HT binding sites, but it remains to be established whether these sites represent a single receptor population.
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PMID:A comparative autoradiographic study of 5-HT1D binding sites in human and guinea-pig brain using different radioligands. 816 19

In human cortex and hippocampus area, [3H]5-HT (5 nM) labels 5-HT1A, 5-HT1D and 5-HT1E sites. After masking 5-HT1A receptors by 0.1 microM 8-OH-DPAT, the binding displaced by 0.1 microM 5-CT presumably represented 5-HT1D sites and the remaining binding 5-HT1E sites. In frontal cortex, 5-HT1A receptors represented the main binding in layers II and VI and a lower fraction in other layers. 5-HT1D and 5-HT1E sites, were more homogeneously distributed in layers II to VI (21-34% of specific [3H]5-HT binding). 5-HT1E sites were of similar affinities (KD close to 6-8 nM) in the cortical layers II to VI. In CA1 field of hippocampus, (pyramidal layer, stratum radiatum, molecular layer), CA2 and dentate gyrus, 5-HT1A receptors represented the major fraction, 5-HT1D sites a significant fraction and 5-HT1E a minor fraction of the specific [3H]5-HT binding. In CA3-CA4 fields, 5-HT1A receptors were less densely present, 5-HT1D sites were predominant and 5-HT1E sites represented a significant fraction (27%). The highest densities of 5-HT1E sites have been measured in subiculum, where 5-HT1A, 5-HT1D and 5-HT1E binding sites were equally represented and in entorhinal cortex where 5-HT1E sites represented the major binding in layer III. They were also present in layers II and IV (29 and 24%) and, to a lesser extent, in layers V and VI. 5-HT1A sites were predominant in layer VI, II and V and were less abundant in other layers. 5-HT1D were homogeneously present in layers II, III, IV and were present in low amounts in other layers. No 5-HT1E were detected in choroid plexus, where [3H]5-HT was dramatically reduced by mesulergine (5-HT2C receptors). No significant displacement of [3H]5-HT by mesulergine was measured in other structures.
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PMID:Quantitative autoradiography of 5-HT1D and 5-HT1E binding sites labelled by [3H]5-HT, in frontal cortex and the hippocampal region of the human brain. 819 79

The effects of 5-HT1A antagonists spiperone, methiothepin and BMY 7378 on [3H]-8-OH-DPAT binding were determined in vitro and ex vivo in rat hippocampus CA3 membrane preparations, and ex vivo in tissue sections of CA1 and CA3 subfields using quantitative autoradiography. In CA3 membranes from rats sacrificed 1 h or 24 h after administration of 5 mg/kg i.p. spiperone or methiothepin, no decrease in [3H]-8-OH-DPAT Bmax values approached statistical significance. Autoradiograms from identically treated rats showed significant increases in Kd values in both CA1 and CA3 hippocampal subfields 24 h but not 1 h after administration of the drugs, while no changes were observed in the dorsal raphe at either time. In vitro co-incubation of membranes with spiperone (200 or 500 nM) or methiothepin (500 nM) resulted in significant decreases in both affinity and Bmax values. In contrast, co-incubation with BMY 7378 (5 nM) increased only Kd values. GTP gamma S produced a concentration-dependent inhibition of specific [3H]8-OH-DPAT binding. At 0.1 mM of GTP gamma S, Kd values were increased three-fold and Bmax values were significantly decreased. When membranes were co-incubated with GTP gamma S and spiperone or BMY 7378, Kd values increased further. Moreover, the effects of spiperone and GTP gamma S on Bmax values were additive. It is concluded that BMY 7378 acts as a competitive antagonist at hippocampal post-synaptic 5-HT1A receptors, whereas spiperone and methiothepin exert their delayed antagonistic effects at these receptors through a non-competitive mechanism of action, possibly affecting the coupling of the receptors to their Gi/o proteins.
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PMID:Delayed effects of spiperone on serotonin1A receptors in the dorsal hippocampus of rats. 829 25

The interactions between 14 days of repeated restraint stress and daily administration of imipramine or tianeptine (2 h before the beginning of stress) were investigated in rats to assess responses of 5-HT2 and 5-HT1A receptors and serotonin transporter sites labelled by [3H]paroxetine in the cerebral cortex and hippocampus, two brain regions in which adrenal steroid effects on serotonin receptor-binding have been reported. 5-HT2 sites, labelled by [125I]7-amino-8-iodo ketanserin, were decreased in parietal cerebral cortex layers 3 and 5 by imipramine treatment, but not by tianeptine treatment and not by daily restraint stress. Stress, but not antidepressant, depressed 5-HT1A sites labelled with [3H]8-hydroxy-DPAT in hippocampal fields CA3, CA4 and dentate gyrus. [3H]paroxetine-binding to serotonin transporter sites was decreased by tianeptine treatment as well as by imipramine in both hippocampus and cerebral cortex, with some overlap of the fields that were significantly affected, whereas there were no effects of stress per se and no evidence of a stress x drug interaction. These results are discussed in relation to similarities and differences in the effects of different antidepressant drugs on the serotonergic system of the rat brain. Whereas the actions of imipramine and tianeptine on 5-HT2 and 5-HT1A receptors are specific to each drug, the surprising finding of a similar effect of both drugs to reduce serotonin transporter sites labelled by [3H]paroxetine suggest the possibility of a common action for these two drugs in spite of their opposite effects on serotonin re-uptake.
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PMID:Stress and antidepressant effects on hippocampal and cortical 5-HT1A and 5-HT2 receptors and transport sites for serotonin. 836 29


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