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)

The effects of acute or chronic ethanol on serotonin (5-HT)-induced membrane hyperpolarization and inhibition of the slow Ca2(+)-dependent after hyperpolarization (sAHP) were recorded in rat CA1 pyramidal neurons in hippocampal slices using sharp intracellular electrodes. 5-HT (1-100 microM) caused concentration-dependent hyperpolarization of the membrane that was not altered by simultaneous 30 mM ethanol treatment, but blunted by 10 microM buspirone, a weak 5-HT1A agonist. 5-HT (1-30 microM) also partially inhibited (approximately 40%) the sAHP following a burst of five or more action potentials. Initially ethanol (30 mM) alone did not alter the sAHP, but over a period of 38 min, a slow increase in amplitude (approximately 40%) was observed. 5-HT-mediated inhibition of the sAHP was significantly greater with ethanol present, regardless of the length of exposure. Pyramidal neurons in hippocampal slices prepared from ethanol-dependent animals showed no obvious signs of withdrawal related hyperexcitability and neither concentration-dependent membrane hyperpolarization nor sAHP inhibition caused by 5-HT were significantly changed from responses in controls. These results suggest that hyperpolarizing responses to 5-HT in hippocampal CA1 pyramidal neurons are functionally resistant to acute or chronic ethanol treatment. 5-HT-mediated inhibition of the sAHP is enhanced by ethanol acutely, but does not show an adaptive change as a result of ethanol dependence.
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PMID:Acute and chronic actions of ethanol on CA1 hippocampal responses to serotonin. 888 49

The effect of 5-HT and its 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on excitatory transmission in CA1 pyramidal cells was studied. Using concentrations of 5-HT within a range of 10-50 microM we observed no change in excitatory postsynaptic potentials (EPSPs) in CA1 cells evoked by Schaffer collateral stimulation. However, at higher concentrations, > or = 100 microM, 5-HT caused a significant decrease (30-40%) in EPSP/Cs, an effect that was also mimicked by 50 microM 8-OH-DPAT. A presumed presynaptic Ca2+ entry was measured in stratum radiatum following repetitive stimulation of the Schaffer collaterals with all excitatory synaptic transmission blocked. Both 5-HT and 8-OH-DPAT reduced this Ca2+ entry. These results suggest that 5-HT acts at presynaptic 5-HT1A receptors to reduce Ca2+ entry and thereby glutamatergic synaptic transmission.
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PMID:Serotonin and 8-OH-DPAT reduce excitatory transmission in rat hippocampal area CA1 via reduction in presumed presynaptic Ca2+ entry. 892 88

The brain 5-HT1A receptor system in male wild house mice selected for high and low offensive aggression was investigated by autoradiographic analysis of in situ hybridization and radioligand binding. In high-aggressive mice, characterized by a short attack latency, the rise in plasma corticosterone concentration during the early dark phase was reduced. At that time the level of 5-HT1A mRNA in the dorsal hippocampus (dentate gyrus and CA1) was twice the amount measured in low-aggressive mice that had long attack latency and high plasma corticosterone level. Increased postsynaptic 5-HT1A receptor radioligand binding was found in dentate gyrus, CA1, lateral septum, and frontal cortex. No difference in ligand binding was found for the 5-HT1A autoreceptor on cell bodies in the dorsal raphe nucleus. In conclusion, genetic selection for high offensive aggression co-selects for reduced (circadian peak) level in plasma corticosterone and increased postsynaptic 5-HT1A receptor number in limbic and cortical regions.
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PMID:Enhanced 5-HT1A receptor expression in forebrain regions of aggressive house mice. 893 Mar 40

The effect of repeated treatment with various antidepressant drugs on the reactivity of CA1 neurons to the 5-HT4 receptor agonist zacopride was examined. Zacopride decreased the calcium-activated afterhyperpolarization and adaptation, it also elicited a slow membrane depolarization associated with an increase in input resistance. All those effects may have contributed to the zacopride-induced increase in the amplitude of population spikes, evoked in the CA1 cell layer by stimulation of the Schaffer collateral/commissural pathway. The later effect of zacopride was concentration-dependent and was antagonized by the 5-HT4 receptor antagonist DAU 62805. Repeated (14 days, twice daily), but not single, administration of the antidepressant drugs imipramine, citalopram, fluvoxamine and paroxetine (10 mg/kg) attenuated the effect of zacopride on population spikes. Because inhibitory 5-HT1A and excitatory 5-HT4 receptors are colocalized on pyramidal neurons, and our previous data demonstrated an increase in the 5-HT1A receptor-mediated inhibition after repeated treatment with antidepressants, we conclude that treatment with antidepressant drugs may enhance the inhibitory effect of 5-HT directly, by increasing the 5-HT1A receptor responsiveness, and indirectly, by inducing subsensitivity to the 5-HT4 receptor activation.
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PMID:Repeated treatment with antidepressant drugs induces subsensitivity to the excitatory effect of 5-HT4 receptor activation in the rat hippocampus. 900 37

The seizure susceptibility in genetically epilepsy prone rats (GEPRs) is reported to be caused by abnormalities in several neurotransmitter systems including the serotonergic system. Among the reported abnormalities is a decrease in brain serotonin content. Therefore, we examined the effects of exogenous serotonin on brain slices from the severe seizure strain of GEPRs (GEPR-9s). We employed conventional electrophysiological techniques to record from CA1 pyramidal neurons of hippocampi of GEPR-9s. The membrane resting potential and input resistance of the GEPR-9 CA1 pyramidal neurons were not different from those of the Sprague-Dawley rats. Serotonin (20 microM) inhibited the directly and synaptically evoked action potentials in GEPR-9 CA1 neurons, as it did in the Sprague Dawley neurons, but only in some and not all of the neurons tested (blocked the directly evoked potentials in 57% and synaptically evoked potentials in 33.3% of the total neurons). This inhibition was also accompanied by hyperpolarization and reduction of membrane input resistance. In the bicuculline-treated brain slices of the GEPR-9, serotonin inhibited the epileptiform bursts causing concurrent hyperpolarization and reduction in membrane input resistance. The effects of the selective serotonin 5-HT1A receptor agonist, 8-OH-DPAT (20 microM) on GEPR-9 pyramidal CA1 neurons were similar to those of serotonin, except the magnitude of hyperpolarization and reduction of membrane input resistance were less than those produced by serotonin. We conclude that the apparent decrease in sensitivity of the GEPR-9 CA1 pyramidal neurons to serotonin may represent a deficiency of serotonin 5-HT1A receptor.
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PMID:Effects of serotonin on induced epileptiform activity in CA1 pyramidal neurons of genetically epilepsy prone rats. 901 48

To clarify the serotonergic mechanisms involved in the protection against ischemic neuronal damage, ZD-211 (citalopram HBr), a serotonin (5-hydroxytryptamine; 5-HT) re-uptake inhibitor, or buspirone, a 5-HT1A agonist, was locally administered into the hippocampus of gerbils. Additionally, to clarify the role of the 5-HT nervous system in the hippocampus during ischemic neuronal damage, animals were subjected to the local administration of 5,7-dihydroxytryptamine (5,7-DHT), a 5-HT neurotoxin, before ischemia challenge. Gerbils received intrahippocampal administration of ZD-211 (200 nmol/animal) or buspirone (20 nmol/animal) before 5-min ischemia. 5,7-DHT was intrahippocampally administered 7 days before a 2-min non-lethal ischemia challenge. In vehicle-treated animals subjected to 5 min of ischemia, almost all hippocampal CA1 pyramidal neurons were lost. The treatment with ZD-211 or buspirone showed a significant protective effect, and the number of neurons was significantly increased compared to vehicle-treated animals. Pretreatment with NAN-190, a 5-HT1A antagonist, completely abolished the protective effect of ZD-211 or buspirone. In the 5,7-DHT-treated animals, the number of neurons was significantly reduced following 2 min of ischemia compared to vehicle-treated animals in which this period of ischemia is non-lethal. Thus, intrahippocampal treatment with ZD-211 or buspirone can protect neuronal damage following transient ischemia in gerbils. These effects of ZD-211 and buspirone were mediated through the 5-HT1A receptor in the hippocampus. Furthermore, the destruction of the 5-HT nervous system in the hippocampus aggravated ischemic neuronal damage. Therefore, this study showed that the enhanced activity of the 5-HT nervous system in the hippocampus may protect against neuronal damage following cerebral ischemia.
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PMID:Role of hippocampal serotonergic neurons in ischemic neuronal death. 906 88

1. Behavioral responses to unilateral and bilateral microinjections of the 5-HT1A receptor antagonist, NAN190 [1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl]piperazine hydrobromide] (1 microgram), into the hippocampal CA1 area of male Wistar rats were studied. 2. NAN190 decreased locomotor activity (the number of horizontal and vertical movements). The effect was most pronounced with microinjections of NAN190 into the right hippocampus. 3. Microinjections of NAN190 facilitated learning and memory in shuttle-box testing. 4. Microinjections of NAN190 had an anxiogenic effect in elevated plus-maze experiments and Vogel's conflict test. 5. The different behavioral responses to left and right microinjections of NAN190 in some of the behavioral tests suggest functional asymmetry of 5-HT1A receptors in the CA1 hippocampal area.
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PMID:Behavorial responses to the 5-HT1A receptor antagonist NAN190 injected into rat CA1 hippocampal area. 906 87

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

The effects of acute and repeated treatment with the 5-HT1A receptor ligand ipsapirone on hippocampal excitatory synaptic transmission and in an ultrasonic vocalization anxiety test were investigated in the rat. Synaptic responses in the CA1 region of the dorsal hippocampus of alert, freely behaving male Wistar rats were reduced after acute injection of ipsapirone (1 or 2 mg/kg, i.p.). This effect was prevented by pretreatment with the 5-HT1A receptor antagonist WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide trihydrochloride, 0.25 or 0.5 mg/kg, i.p.) but not by the 5-HT-depleting agent para-chlorophenylalanine (300 mg/kg per day for 3 days, i.p.). WAY-100635 (0.1-0.3 mg/kg, i.p.) also blocked the acute anti-aversive effects of ipsapirone (3 mg/kg, i.p.) in the anxiety test. Repeated administration of ipsapirone (1 or 2 mg/kg per day for 7-8 days, i.p.) produced a gradual reduction in baseline synaptic transmission which was transiently reversed by WAY-100635 (0.25 mg/kg, i.p.). Ipsapirone (1 mg/kg per day for 7 days) produced a gradual and sustained reduction in the duration of vocalizations in the anxiety test which paralleled the reduction in baseline synaptic responses in the same animals. The data indicate that with repeated administration of ipsapirone, a prolongation and enhancement of the 5-HT1A receptor-mediated reduction in hippocampal excitatory synaptic transmission occurs. This delayed effect may contribute to the sustained anxiolytic and/or antidepressant effect of ipsapirone.
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PMID:Effect of repeated ipsapirone treatment on hippocampal excitatory synaptic transmission in the freely behaving rat: role of 5-HT1A receptors and relationship to anxiolytic effect. 910 77

The receptor binding and pharmacological profile of the new, putative 5-HT1A receptor antagonist MP-3022 (4-[3-(benzotriazol-1-yl)propyl]-1-(2-methoxyphenyl)piperazine) were studied. Another 5-HT1A receptor antagonist, (S)-WAY 100135 ((S)-N-tert-butyl-3-[4-(2-methoxyphenyl)piperazine-1-yl]-2- phenylpropanamide), was used as a reference drug in functional models. MP-3022 showed a high affinity (Ki) of 25 nM and 69 nM, respectively, at 5-HT1A binding sites and alpha 1-adrenoceptors in vitro. The Ki values of MP-3022 in relation to other binding sites examined (5-HT2A, alpha 2- or beta-adrenoceptors, dopamine D1 and D2) were 20-100-fold lower. In functional studies, MP-3022 significantly attenuated the 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin)-induced decrease in the population spike evoked in the CA1 cell layer of the hippocampal slice preparation, without producing its own effects. The 8-OH-DPAT-evoked increase in the corticosterone concentration in the serum as well as the 8-OH-DPAT-mediated decrease in the 5-HT turnover in the hippocampus were attenuated by MP-3022. MP-3022 increased the serum corticosterone concentration only at the highest dose used, but it did not change the 5-HT turnover in the hippocampus. Like MP-3022, (S)-WAY 100135 antagonized the 8-OH-DPAT-induced effects. It has also been demonstrated that (S)-WAY 100135 is devoid of an intrinsic activity at 5-HT1A receptors. The data obtained demonstrate that, like (S)-WAY 100135, MP-3022 behaves like a functional antagonist at pre- and postsynaptic 5-HT1A receptors.
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PMID:MP-3022, a new putative antagonist at pre- and postsynaptic 5-HT1A receptors. 911 23


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