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

Corticosterone (CT) treatment decreases the magnitude of the 5-hydroxytryptamine (5-HT)1A receptor-mediated hyperpolarization in rat CA1 hippocampal pyramidal neurons. In the present study, we examined the short- and long-term effects of CT on the functionally excitatory 5-HT4 receptor-mediated decrease in the amplitude of the slow afterhyperpolarization (sAHP) that follows a calcium spike and the concomitant decrease in sAHP half decay time. Rats were adrenalectomized (ADX) 2 weeks before the experiment. Data for concentration-response curves were obtained with sharp electrode current clamp recordings in the CA1 pyramidal cell layer of hippocampal slices. Significant changes were found in the 5-HT4 receptor-mediated decrease in sAHP amplitude. The Emax of the 5-HT4 response was significantly increased in cells from ADX rats when the superfusion medium contained 1 nM CT. Short-term administration of 100 nM CT did not alter the 5-HT4 response. Chronic treatment with low concentrations of CT decreased the Emax of the 5-HT4 response. Treatment with CT concentrations that mimic conditions of chronic stress decreased the Emax of the 5-HT4 response and shifted the EC50 to the right. Based on these results we conclude that the magnitude and the potency of the 5-HT4 receptor-mediated decrease in sAHP amplitude is altered by CT. Because the short- and long-term effects of CT treatment are not the same, the actions of CT are time and concentration dependent. CT modulation of the 5-HT4 response is different from its modulation of the 5-HT1A response.
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PMID:Modulation of the 5-hydroxytryptamine4 receptor-mediated response by short-term and long-term administration of corticosterone in rat CA1 hippocampal pyramidal neurons. 779 Oct 83

We have examined the distribution of 5-HT1A and 5-HT2A receptor mRNAs in post-mortem human hippocampus, neocortex, raphe nuclei, cerebellum and basal ganglia using in situ hybridization histochemistry. Receptor transcripts in brains from two males and two females (mean age +/- S.D. = 70 +/- 4 years; post-mortem interval = 29 +/- 6 h) were visualised with 35S-radiolabelled synthetic oligodeoxyribonucleic acid probes. In the hippocampus, 5-HT1A receptor mRNA was present in all fields, especially CA1. In the parahippocampal gyrus and neocortical regions 5-HT1A receptor mRNA was enhanced in superficial and middle laminae. 5-HT1A receptor mRNA was particularly abundant in the raphe and other serotonergic cell groups of the brainstem. The analysis of emulsion dipped sections showed 5-HT1A receptor mRNA to be concentrated in pyramidal neurons, together with the granule cells of the dentate gyrus. In neocortical areas lamina III pyramidal neurons were more heavily labelled than those in lamina V. There was no evidence of glial expression of 5-HT1A receptor mRNA in grey matter or white matter compartments. 5-HT2A receptor mRNA was present in all neocortical areas examined, where it was located in pyramidal neurons, of lamina V more than in those of lamina III, as well as in putative interneurons, especially within lamina IVc of the striate cortex. 5-HT2A receptor mRNA was observed at minimal levels in the hippocampus and not in the raphe. Neither 5-HT1A nor 5-HT2A receptor mRNA were detected in the cerebellum, substantia nigra or striatum. The ability to detect these transcripts at the regional and cellular level will help reveal important details of the 5-HT receptor system in the human brain. This includes the investigation of their putative roles in the normal chemoarchitecture and in pathophysiological brain processes.
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PMID:The distribution of 5-HT1A and 5-HT2A receptor mRNA in human brain. 779 65

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

Previous studies have shown that adrenalectomy (ADX) increases the binding of 3H-DPAT to 5-HT1A receptors in the hippocampus (HIP) and this effect is partially overcome by corticosterone (CORT) replacement. The present study investigated the time course of the effects of ADX with or without CORT replacement on serotonin (5-HT) pre- and postsynaptic systems in the HIP and dorsal raphe nucleus (DR) by quantitative autoradiography. In the HIP, ADX for 7, 10 or 14 days caused a significant increase in 3H-DPAT binding in the CA1 region (pyramidal layer), CA2,3 region (molecular and pyramidal layers) and in the dentate gyrus (molecular and granular layers) which returned to control levels when measurements were made 35 days post-ADX. A decrease in 3H-DPAT binding was observed 14 days after ADX in the DR but not in the median raphe nucleus (MR). Although replacement with CORT did not lead to a reversal in 3H-DPAT binding early time points, binding was restored to control levels 7-28 days after CORT replacement in all regions of the HIP. In the DR, CORT did not cause a reversal in 3H-DPAT binding at any of the time points examined. In contrast to the effects seen on the 5-HT1A receptor subtype, no significant change was noted on the binding of 3H-CN-IMI to uptake sites for 5-HT in the HIP or DR after ADX or CORT replacement. The results of this study indicate that long-term alterations in the HPA axis lead to changes in the 5-HT1A receptor system that are both region-specific and time-dependent.
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PMID:Time course of the effects of adrenalectomy and corticosterone replacement on 5-HT1A receptors and 5-HT uptake sites in the hippocampus and dorsal raphe nucleus of the rat brain: an autoradiographic analysis. 786 63

The present study examined the behavioral responses of rats to unilateral and bilateral injections of the selective serotonin 1A (5-HT1A)-receptor agonist 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT) 1 microgram into the hippocampal CA1 area of male Wistar rats. 8-OH-DPAT increased locomotor activity, which was most pronounced with injections into the left hippocampus. The agonist impaired learning and memory (shuttle-box), especially when injected into the right hippocampus. The elevated plus-maze experiments showed that neither left nor right nor bilateral hippocampal injections of 8-OH-DPAT produced any anxiogenic effect. However, with Vogel's conflict test, right injections of 8-OH-DPAT produced anxiety. The present study has revealed hippocampal asymmetry in the behavioral responses to the 5-HT1A-receptor agonist 8-OH-DPAT.
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PMID:Hippocampal asymmetry in the behavioral responses to the 5-HT1A receptor agonist 8-OH-DPAT. 791 27

The effect of dexamethasone, a selective GR agonist, on hippocampal, 5-HT1A receptor mRNA expression and 5-HT1A binding was examined using in situ hybridization histochemistry and in vitro receptor autoradiography. One week after adrenalectomy, both 5-HT1A receptor mRNA expression and 5-HT1A binding were increased throughout the hippocampus. Administration of dexamethasone at the time of adrenalectomy significantly attenuated the increases in 5-HT1A mRNA expression in all hippocampal subfields (p < .05, Fisher Test), although 5-HT1A mRNA levels remained significantly higher than sham levels in all subfields with the exception of CA1. However, 5-HT1A binding levels were responsive to dexamethasone administration only within particular hippocampal subfields, CA1, and dentate gyrus. We conclude that GR occupation negatively regulates 5-HT1A receptor mRNA expression within the hippocampus and that 5-HT1A receptor sites are most sensitive to modulation in those hippocampal subfields expressing higher levels of GR receptors.
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PMID:Regulation of hippocampal 5-HT1A receptor gene expression by dexamethasone. 791 19

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

1. The effect of acute and repeated treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor ligand, on excitatory amino acid-mediated synaptic transmission was examined in the stratum radiatum CA1 region of the dorsal hippocampus of alert, gently restrained, rats. 2. Acute administration of 8-OH-DPAT transiently reduced the amplitude of the field excitatory postsynaptic potential (e.p.s.p.) in a dose-dependent (25-75 micrograms kg-1, i.p.) manner. This effect was blocked by the postsynaptic 5-HT1A receptor antagonist, MDL 73005EF (2 and 4 mg kg-1, i.p.). 3. 8-OH-DPAT (25 micrograms kg-1, i.p.) administered daily for 7 days produced a gradual reduction in the 24 h pre-injection baseline field e.p.s.p. amplitude. The reduction reached its lowest level after 7-8 days and was transiently reversed by acute injection of MDL 73005EF (2 mg kg-1, i.p.) on day 8. The field e.p.s.p. baseline amplitude recovered fully 5-8 days after cessation of drug treatment. 4. 8-OH-DPAT (25 micrograms kg-1, i.p.) administered daily for 7 days produced a marked reduction in acute response to 8-OH-DPAT (25 and 50 micrograms kg-1, i.p.) which did not recover until between day 36 and day 80 of the study. 5. It was concluded that repeated treatment with 8-OH-DPAT produced adaptive changes which resulted in a reduction in the dynamic range of 5-HT1A receptor-mediated transmission in the hippocampus.
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PMID:Adaptive changes in 5-HT1A receptor-mediated hippocampal inhibition in the alert rat produced by repeated 8-OH-DPAT treatment. 795 67

We recently reported that rats with elevated brainstem serotonin (5-HT) concentration and 5-HT transporter binding site density after neonatal 5,7-dihydroxytryptamine (5,7-DHT) lesions made by intraperitoneal (i.p.) injection exhibited more myoclonic supersensitivity to the 5-HT1A agonist 8-OH-DPAT than those with decreased brainstem 5-HT and 5-HT transporter sites following intracisternal 5,7-DHT (i.c.) injection. To investigate the role of 5-HT1A receptors in these differences, we labelled 5-HT1A binding sites autoradiographically with [3H]8-OH-DPAT 4 months after i.p. or i.c. 5,7-DHT or saline in the first week postnatal. The regional distribution of 5-HT1A sites conformed to previous reports of highest receptor densities in hippocampus (CA1, dentate gyrus), septal nuclei, dorsal and median raphe, mammillary body, and certain cortical regions (cingulum, claustrum). 5-HT1A binding was significantly decreased (-87%) in the dorsal raphe after i.c.-made 5,7-DHT lesions. No reductions were found after lesions made by i.p. injection compared to controls, but rather a 246% increase in area of 5-HT1A binding extending from the dorsal raphe was observed. These changes in 5-HT1A binding sites in the dorsal raphe in the chronic phase of 5,7-DHT lesions may contribute to the different behavioral consequences of the route of neonatal 5,7-DHT injection.
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PMID:Quantitative autoradiography of 5-hydroxytryptamine1A binding sites in rats with chronic neonatal 5,7-dihydroxytryptamine lesions. 795 34


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