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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of 5-HT3 receptor agonists and antagonists on the hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 field potential elicited by stimulation of Schaffer collaterals was investigated using rat hippocampal slices. Treatment with the 5-HT3 receptor agonist, 2-methyl-5-HT (1-10 microM), exacerbated the ischemia-induced decreased in CA1 field potential, whereas treatment with the 5-HT3 receptor antagonist, Y-25130 (0.1-100 microM), or the 5-HT2 receptor antagonist, ketanserin (10, 100 microM), produced dose-dependent neuroprotection against the ischemia-induced decrease. However, in normal non-ischemic solution these treatments did not significantly change the CA1 field potential. The protective action of Y-25130 was blocked by co-treatment with 2-methyl-5-HT. The magnitude of protection in the Y-25130-treated group (EC50, 1.8 microM) was about 20 times greater than that in the ketanserin-treated group (EC50, 33 microM). The present study demonstrated that stimulation of 5-HT3 receptors plays a detrimental role in the development of ischemic damage, whereas blockade of the 5-HT3 receptor plays a neuroprotective role in ischemic damage, suggesting a facilitatory role of 5-HT neurons in ischemia-induced neuronal deficits.
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PMID:Neuroprotective effect of 5-HT3 receptor antagonist on ischemia-induced decrease in CA1 field potential in rat hippocampal slices. 145 43

1. The effect of serotonin on inhibitory synaptic transmission was examined in forty-one CA1 pyramidal neurones using intracellular voltage recordings in vitro. 2. Serotonin (20-50 microM) increased the synaptic noise of most (85%) neurones loaded with chloride (n = 33). The duration of this effect was enhanced with increasing concentrations of serotonin and was fully reversible within 5 min. When serotonin was applied at short intervals (less than 10 min), fading of the response was observed. 3. The effect of serotonin on synaptic noise persisted in the presence of the glutamate NMDA and non-NMDA antagonists, APV (100 microM) and CNQX (10 microM), but it was blocked (n = 5) by a GABAA antagonist, bicuculline (10 microM). 4. The increase in inhibitory synaptic events resulted from an enhanced frequency of unitary IPSPs from 4.6 +/- 3.8 Hz in control to 17.2 +/- 12.5 Hz (n = 5) in serotonin, especially of large events. Serotonin caused no change in the amplitude and frequency of miniature synaptic events recorded in the presence of TTX (n = 5). The mean amplitude of unitary inhibitory postsynaptic potentials (IPSPs) increased from 1.37 +/- 0.35 mV in control to 3.67 +/- 1.38 mV in serotonin. The coefficient of variation of unitary IPSPs increased from 0.40 +/- 0.11 in control to 0.74 +/- 0.23 in serotonin when quantal size appeared unchanged. 5. The 5-HT3 agonist 2-methyl-serotonin (52 microM, n = 4) partially mimicked the effect of serotonin, increasing the inhibitory noise without affecting the pyramidal neurone conductance. The serotonin-induced facilitation of unitary IPSPs was blocked by the 5-HT3 antagonists ICS 205-930 (1-90 nM, n = 3) and metoclopramide (30 microM, n = 1). 6. These results suggest that serotonin directly excites GABAergic interneurones acting on a 5-HT3 receptor and consequently increasing the frequency of inhibitory synaptic events recorded in CA1 pyramidal cells.
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PMID:Serotonin facilitates GABAergic transmission in the CA1 region of rat hippocampus in vitro. 168 46

Serotonergic brainstem projections to hippocampus are thought to preferentially target and increase, via 5-HT3 receptors, the excitability of a distinct subpopulation of interneurons that primarily regulate GABAB-mediated inhibition in the dendritic region of pyramidal cells. Hippocampal slice work suggests that the between-burst hyperpolarization caused by slow (GABAB) IPSPs plays a significant role in controlling the strength of LTP induced with theta burst stimulation. According to the above observations it was assumed that blockade of hippocampal 5-HT3 receptors should reduce the hyperpolarization and thereby enhance both the frequency of the naturally occurring theta rhythm and the induction of LTP; moreover, if LTP-like mechanisms provide the substrate for certain forms of memory, such treatment was expected to facilitate learning. Each of the above predictions was tested and confirmed in the present set of experiments. The effects of ondansetron, a potent and selective antagonist of the 5-HT3 receptor, were examined on (1) frequency of the hippocampal theta rhythm, (2) induction of LTP in field CA1 of freely moving rats, and (3) retention of olfactory and spatial memory in tasks known to depend on an intact hippocampus. When injected intraperitoneally into freely moving rats, the drug reliably and significantly increased the frequency of the hippocampal theta rhythm in a dose-dependent manner. Second, at concentrations that facilitate theta frequency (100 micrograms/kg and 500 micrograms/kg), an injection of the drug 30 min prior to delivering electrical stimulation bursts significantly increased the magnitude and duration of LTP compared to that obtained in the same animals after vehicle injections.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of 5-HT3 receptor antagonism on hippocampal theta rhythm, memory, and LTP induction in the freely moving rat. 789 Nov 79

The effects of the serotonin (5-HT)3 receptor agonist, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT), were studied in CA1 pyramidal cells of the rat hippocampus in vitro using the whole cell gigaseal technique. 2-Methyl-5-HT (10 and 50 microM) did not change significantly the electrophysiologic properties of the cells but reversibly reduced excitatory and inhibitory postsynaptic potentials evoked by stimulation of the Schaffer collaterals. The onset and termination of this effect was in the order of minutes and no desensitization was observed. The selective 5-HT3 receptor antagonist, granisetron, when applied as a pretreatment completely prevented but did not reverse this action when given after administration of 2-methyl-5-HT while the non-specific 5-HT1,2 receptor antagonist, metergoline, was ineffective. These results suggest that the activation of 5-HT3 receptors reduces the efficacy of glutamatergic synaptic transmission in this area.
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PMID:The 5-HT3 receptor agonist 2-methyl-5-HT reduces postsynaptic potentials in rat CA1 pyramidal neurons of the hippocampus in vitro. 792 84

The techniques of extracellular single cell recording and microiontophoresis were used to study the effect of 5-HT3 receptor agonists on glutamate-activated firing of CA1 hippocampal pyramidal cells. Iontophoretic application of 5-HT3 receptor agonists 2-methyl-5-HT and SR 57227A produced a current (dose)-dependent suppression of the firing of CA1 pyramidal cells; SR 57227A was more effective than 2-methyl-5-HT. The suppressant action of 2-methyl-5-HT and SR 57227A had a slow onset and showed little or no desensitization. This effect was markedly attenuated or completely blocked by the 5-HT3 receptor antagonist BRL 46470A but not by the nonspecific 5-HT1 and 5-HT2 receptor antagonist metergoline or by the 5-HT1A antagonist WAY 100478. Intravenous administration of SR 57227A was effective in reducing the firing rate of CA1 pyramidal cells and this effect was prevented by BRL 46470A administered either i.v. or iontophoretically. Iontophoresis of 2-methyl-5-HT also diminished CA1 postsynaptic field potentials evoked by electrical stimulation of the Schaffer collaterals. Again, BRL 46470A but not metergoline prevented the suppressant action of 2-methyl-5-HT. Taken together, our results indicate that activation of 5-HT3-like receptors in the hippocampal CA1 region effectively reduces the efficacy of glutamatergic neurotransmission.
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PMID:Serotonin3 receptor agonists attenuate glutamate-induced firing in rat hippocampal CA1 pyramidal cells. 798 87

The serotonin 5-HT3 receptor subtype has been implicated in many brain functions. Antagonists of this receptor have anxiolytic and antiemetic effects in humans and in animal models. To determine with cellular resolution the distribution of 5-HT3 receptor mRNA, in situ hybridization was performed in sections of mouse brain and dorsal root ganglia. Scattered labeled cells were observed throughout cortical regions, with highest densities in the piriform, cingulate, and entorhinal areas. Strong hybridization signals were seen in the hippocampal formation, where expression appeared primarily in interneurons. Labeled cells were most abundant in the posteroventral hippocampal region, particularly in the lacunosum moleculare layer of CA1. This distribution suggests that 5-HT3 receptors may mediate the known serotonergic inhibition of pyramidal cell populations via excitation of inhibitory interneurons. Labeled cells were also observed in the major subdivisions of the amygdaloid complex, the olfactory bulb, the trochlear nerve nucleus, the dorsal tegmental region, the facial nerve nucleus, the nucleus of the spinal tract of the trigeminal nerve, and the spinal cord dorsal horn. In the periphery, intense hybridization signals were seen in a subpopulation of cells in dorsal root ganglia. The data correlate generally with physiological, behavioral, and receptor autoradiographic studies, provide cellular resolution, and reveal regions of receptor expression not previously observed. The distribution of 5-HT3 receptor mRNA is consistent with roles for the receptor in cognition and affect and in the modulation of sensory input.
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PMID:Nervous system distribution of the serotonin 5-HT3 receptor mRNA. 843 3

Intra- and extracellular recordings from the in vitro rat hippocampal slice preparation have been used to investigate the influence of serotoninergic, adrenergic and cholinergic receptor antagonists on the excitability of CA1 pyramidal neurones. The serotonin receptor antagonist 4-amino-N-(1-azabicyclo[2.2.2]oct-3yl)-5-chloro-2- methoxybenzamide(E)-2-butenedioate (zacopride, 100 microM) produced multiple population spikes on the orthodromically evoked field potential, in contrast to the lack of effect of another serotonin antagonist 1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222, 30 microM), as well as the cholinergic antagonists atropine (10 microM) and hexamethonium (100 microM) and the noradrenergic antagonist atenolol (10 microM). Monosynaptic inhibitory postsynaptic potentials (IPSPs) recorded in the presence of the glutamatergic antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and ketamine (50 microM) were recorded from CA1 pyramidal neurones. Zacopride (100 microM) and MDL 72222 (30 microM) both reduced the isolated IPSP to 54 +/- 9% (n = 8) and 78 +/- 4% (n = 3), respectively. Neither of the cholinergic antagonists had any effect, while atenolol reduced the IPSP to 87 +/- 3% (n = 7) of the control IPSP. We propose that the difference in action of zacopride and MDL 72222 on the field potentials is due to zacopride activating postsynaptic 5HT4 receptors on the pyramidal neurone, thereby reducing a Ca(2+)-activated K(+)-conductance. This, in combination with a 5HT3 receptor-mediated reduction in gamma-aminobutyric acid (GABA)-ergic inhibition, leads to an increase in pyramidal cell excitability evident as epileptic field potentials.
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PMID:Serotoninergic modulation of excitability in area CA1 of the in vitro rat hippocampus. 857

To study the role of hippocampal muscarinic receptors in spatial learning, various doses of scopolamine were injected bilaterally into the CA1 region of the dorsal hippocampus of rats trained in a two-platform spatial discrimination task. Scopolamine administered 10 min before each training session at doses ranging from 3.75 to 15 micrograms/microliter impaired choice accuracy, had no effect on choice latency and increased the errors of omission only with 7.5 micrograms on day 1 and with 15 micrograms on days 1 and 2 of training. No dose affected choice accuracy or latency of a non-spatial visual discrimination task. A subcutaneous dose of 1 microgram/kg ondansetron, a 5-HT3 receptor antagonist, 30 min before each training session prevented the impairment of choice accuracy by intrahippocampal 3.75 micrograms scopolamine but 0.1 microgram/kg ondansetron had no such effect. No dose of ondansetron by itself modified the acquisition of spatial learning. The results suggest that relatively low doses of scopolamine in the dorsal hippocampus selectively impair the acquisition of a spatial discrimination task, and that blockade of 5-HT3 receptors prevents the deficit caused by the muscarinic antagonist. The utility of the deficit of spatial learning induced by intrahippocampal scopolamine for modelling some aspects of memory disturbances in Alzheimer's disease is discussed.
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PMID:Dose-related impairment of spatial learning by intrahippocampal scopolamine: antagonism by ondansetron, a 5-HT3 receptor antagonist. 903 Apr

5-Hydroxytryptamine (5-HT; serotonin) administration enhances GABAergic synaptic activity recorded in pyramidal neurons of the CA1 region of hippocampus. Previous studies have attributed this effect to the activation of HT-5(3) receptors located on GABAergic interneurons. During unrelated experiments, we noticed that under our recording conditions, 5-HT can still increase GABAergic synaptic activity after the complete blockade of 5-HT3 receptors. This indicated the involvement of an additional 5-HT receptor subtype. Therefore, we reinvestigated the effects of 5-HT on GABAergic synaptic activity recorded in pyramidal cells of the CA1 region. The ability of 5-HT to increase GABAergic synaptic activity in the presence of 5-HT3 receptor blockade was mimicked by the selective 5-HT2 agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and blocked by the selective 5-HT2 antagonist ketanserin. This indicated that the additional 5-HT receptor belongs to 5-HT2 receptor family. 5-HT2 receptor activation resulted in an increase in the frequency of spontaneous inhibitory postsynaptic currents as well as a shift in their amplitude distribution toward larger sizes. These effects were absent in the presence of tetrodotoxin. We interpret these results to indicate that 5-HT2 receptors activate GABAergic interneurons in the slice, leading to an increase in GABAergic synaptic activity onto pyramidal cells of the CA1 region.
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PMID:5-Hydroxytryptamine2 receptor facilitates GABAergic neurotransmission in rat hippocampus. 958 Jun 30

Considerable evidence exists for an involvement of serotonergic mechanisms in the control of alcohol consumption. In the present study, an extensive 5-hydroxytryptamine (5-HT3) receptor autoradiographical investigation was performed using two genetically selected rat strains, alcohol preferring (P) and Alko alcohol (AA) alcohol-preferring rats, as well as the corresponding alcohol nonpreferring (NP) and Alko nonalcohol (ANA) alcohol-nonpreferring rats. The aim was to determine if there are any differences in 5-HT3 binding levels that may illuminate mechanisms of alcohol preference in these animals. For quantitating 5-HT3 binding sites, [3H]S(-)zacopride (0.5 nM) was used. Non-specific binding was measured in the presence of granisetron 10(-6) M. The [3H]S(-)zacopride binding density was measured in two subregions of the amygdaloid nucleus, frontal cortex, piriform cortex, cingulate laminae, parietal anterior cortex, parietal medial cortex, hippocampus CA1, hippocampus CA3, and entorhinal cortex. In all the brain areas investigated, the results showed no differences between AA and ANA rats. In P rats, compared to NP controls, there was a 30% lower 5-HT3 binding level in the lateral nucleus and the posteromedial cortical nucleus of the amygdala. These findings suggest that the expression of high alcohol preference in genetically selected P and AA rats is not associated with a general alteration of central 5-HT3 receptors, although a lower 5-HT3 receptor level in the amygdala of P rats may contribute to the phenotype of this strain of animals.
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PMID:Central 5-HT3 receptors in P and in AA alcohol-preferring rats: An autoradiographic study. 967 Dec 60


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