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)

1. Autonomous, pacemaker-like activity of serotonergic raphe neurones and its autoregulation by somatodendritic 5-HT1A receptors are well described, but little is known of synaptic inputs onto raphe neurones or their modulation. Therefore, we recorded unitary excitatory postsynaptic currents (EPSCs) in caudal raphe neurones (raphe obscurus and pallidus) following local electrical stimulation in a neonatal rat brainstem slice preparation; most neurones (79 %; n = 72/91) recovered following post hoc immunohistochemistry were tryptophan hydroxylase-immunoreactive, indicating that they were serotonergic. 2. Evoked EPSCs occurred at relatively constant latency with variable amplitude and apparent 'failures' at fixed suprathreshold stimulus intensity. At -60 mV, EPSCs were wholly due to CNQX-sensitive, non-NMDA glutamate receptors; at depolarized potentials, a small AP-5-sensitive NMDA component was often observed. 3. EPSCs were potently and reversibly inhibited by 5-HT with an EC50 of 0.1 microM. This effect was mimicked by 5-HT1B agonists (CP-93,129 and anpirtoline), but not by a 5-HT1A agonist (8-OH-DPAT), indicating that 5-HT1B receptors mediate the inhibition of EPSCs. 4. Multiple lines of evidence indicate that inhibition of EPSCs by 5-HT was mediated presynaptically. First, currents evoked by exogenous glutamate application were unaffected by 5-HT and/or 5-HT1B agonists. In addition, the frequency of spontaneous glutamatergic miniature EPSCs was diminished by CP-93,129 and paired-pulse facilitation of EPSCs was enhanced by 5-HT. Finally, the 5-HT1B receptor agonists that blocked synaptic transmission had no effect on resting membrane properties of raphe neurones. 5. These data indicate that serotonergic caudal raphe neurones receive glutamatergic inputs that are inhibited by presynaptic 5-HT1B receptors; inhibition of excitatory synapses onto raphe cells may represent a novel mechanism for autoregulation of serotonergic neuronal activity by 5-HT.
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PMID:Presynaptic inhibition by 5-HT1B receptors of glutamatergic synaptic inputs onto serotonergic caudal raphe neurones in rat. 962 71

Stimulus control was established in a group of seven rats using a dose of KA 672 [7-methoxy-6-[3-[4-(2-methoxyphenyl)-1-piperazinyl] propoxy]3,4-dimethyl-2H-1-benzopyran-2-one HCl] of 1.0 mg/kg, administered i.p., 15 min before training. A two-lever operant task using a fixed-ratio 10 schedule of sweetened milk reinforcement was used. Based upon a criterion for the presence of stimulus control of five consecutive sessions during which 83% or more of all responses were on the appropriate lever, a mean of 23 sessions was required to reach criterion performance. Subsequently, it was observed that KA 672-induced stimulus control is partially but significantly antagonized by the selective 5-HT1A antagonist, WAY-100635. Furthermore, KA 672 generalized to the selective 5-HT1A agonist, 8-hydroxy-dipropylaminotetralin [8-OH-DPAT], and this generalization was blocked by WAY-100635. Other tests of generalization were conducted with the structural analogs, scoparone, CD-127, and OMPP, as well as with the receptor-selective ligands ketamine, PCP, dizocilpine, prazosin, urapidil, apomorphine, and DTG. Of these drugs only dizocilpine met the criteria for full substitution while an intermediate level of generalization was observed to ketamine, PCP, urapidil, and apomorphine. The present results indicate that KA 672-induced stimulus control is mediated in part by activity at the 5-HT1A receptor and that behaviorally significant interactions occur as well at PCP/NMDA, dopaminergic, and adrenergic receptors.
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PMID:The discriminative stimulus effects of KA 672, a putative cognitive enhancer: evidence for a 5-HT1A component. 967 54

Photic entrainment of circadian rhythms occurs as a consequence of daily, light-induced adjustments in the phase and period of the suprachiasmatic nuclei (SCN) circadian clock. Photic information is acquired by a unique population of retinal photoreceptors, processed by a distinct subset of retinal ganglion cells, and conveyed to the SCN through the retinohypothalamic tract (RHT). RHT neurotransmission is mediated by the release of the excitatory amino acid glutamate and appears to require the activation of both NMDA- and non-NMDA-type glutamate receptors, the expression of immediate early genes (IEGs), and the synthesis and release of nitric oxide. In addition, serotonin appears to regulate the response of the SCN circadian clock to light through postsynaptic 5-HT1A or 5-ht7 receptors, as well as presynaptic 5-HT1B heteroreceptors on RHT terminals.
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PMID:Photic entrainment of circadian rhythms in rodents. 978 33

The neurotransmitter serotonin (5-HT) induces rhythmic motor patterns (fictive locomotion) of the neonatal rat spinal cord in vitro; this is a useful experimental model to study the generation of a motor programme at exclusively spinal level. Nevertheless, 5-HT slows down the fictive locomotion typically elicited by activation of NMDA glutamate receptors, suggesting a complex action of this monoamine. By means of electrophysiological recordings from multiple ventral roots we demonstrated that the decrease caused by 5-HT in NMDA-induced periodicity was dose-dependent, enhanced after pharmacological blocking of 5-HT2 excitatory receptors, and imitated by pharmacological agonists of the 5-HT1 receptor family. Selective blockers of the 5-HT1A or 5-HT1B/D receptor classes, either alone or in combination, largely (but not completely) attenuated this inhibitory action of 5-HT. It is concluded that the principal inhibitory action of 5-HT on the spinal locomotor network was mediated by certain subtypes of the 5-HT1 receptor class, which tends to oppose the 5-HT2 receptor-mediated excitation of the same network.
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PMID:Serotonin-induced inhibition of locomotor rhythm of the rat isolated spinal cord is mediated by the 5-HT1 receptor class. 984 33

The effects of a single rapid-rate transcranial magnetic stimulation (rTMS) exposure on neurotransmitter binding sites in the rat brain 24 h after the stimulation were examined. Quantification by in vitro-autoradiography showed no differences for 3H-paroxetine binding (5-HT uptake sites) between rTMS-treated, sham and control animals. In contrast, the number of 5-HT1A binding sites (labeled with 3H-8-OH-DPAT) were selectively increased in the rTMS-group with significantly higher BMAX values in the frontal cortex, the cingulate cortex, and the anterior olfactory nucleus. A non-specific increase in NMDA binding sites (labeled with 125I-MK-801) in rTMS and sham animals was observed in the hippocampal formation. A selective increase of these binding sites after rTMS was detected in the ventromedial hypothalamus, the basolateral amygdala and layers 5-6 of the parietal cortex. These findings imply that a single rTMS exposure can result in persistent effects on NMDA and 5-HT1A binding sites even 24 h after stimulation and therefore may be of relevance with respect to the therapeutic action of rTMS reported from clinical studies.
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PMID:Changes in 5-HT1A and NMDA binding sites by a single rapid transcranial magnetic stimulation procedure in rats. 1022 11

This study examined effects of various psychoactive drugs on the Vogel conflict test, where drinking behavior is punished by electric shocks, in ICR mice to clarify the pharmacological features of this method in mice. A benzodiazepine anxiolytic diazepam and a barbiturate pentobarbital produced significant anticonflict effects, which mean that these drugs increased the number of electric shocks mice received during 40-min test session. On the other hand, yohimbine (alpha2-receptor antagonist), caffeine (adenosine-receptor antagonist), scopolamine (muscarinic cholinergic antagonist), cyclazocine (sigma-receptor antagonist), cimetidine (H2-receptor antagonist), baclofen (GABA(B)-receptor agonist), MK-801 (NMDA-receptor antagonist), buspirone (5-HT1A-receptor agonist), chlorpromazine (dopamine-receptor antagonist) and haloperidol (dopamine-receptor and sigma-receptor antagonist) all did not produce anticonflict effects in this test using ICR mice. The results suggest that the Vogel conflict test is applicable to ICR mice and that this test in mice is appropriate as a screening method for drugs that have apparent anti-anxiety actions.
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PMID:Effects of psychoactive drugs in the Vogel conflict test in mice. 1044 May 29

We studied the effect of WAY 100635, a 5-HT1A receptor antagonist, on the impairment of spatial learning caused by intrahippocampal injection of 3-((R)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive NMDA receptor antagonist, in a two-platform spatial discrimination task. CPP, 3 and 10 ng/microl, administered bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, dose-dependently reduced choice accuracy in the two-platform spatial discrimination task with little or no effect on choice latency and errors of omission. A volume of 10 ng/microl intrahippocampal CPP did not affect choice accuracy or latency of a non-spatial visual discrimination task. Subcutaneous doses of 0.3 and 1 mg/kg WAY 100635 did not modify the choice accuracy, but prevented the impairment caused by 10 ng/microl intrahippocampal CPP. A dose of 20 ng/microl WAY 100635 into the dorsal hippocampus prevented the deficit caused by 10 ng/microl CPP administered in the same region. The results suggest that blockade of 5-HT1A receptors can compensate the loss of NMDA-mediated excitatory input to pyramidal cells in the hippocampus. These findings may have clinical relevance for the symptomatic treatment of memory disorders associated with reduced glutamate transmission mediated by NMDA receptors.
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PMID:WAY 100635, a 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by blockade of hippocampal NMDA receptors. 1046 29

The effect of the AMPA antagonist NBQX (10 microM), NMDA antagonist ketamine (100 microM) and 5-HT1A agonist 8-OH-DPAT (1, 10 and 100 microM) on the properties of a KCl-induced spreading depression (SD) was studied in parietal cortical slices of adult rats. Whereas NBQX did not significantly affect the SD, ketamine significantly (p < 0.01) reduced the amplitude of the first SD peak (12.8 +/- 4.6 mV) and blocked the second SD peak when compared with the controls (19.8 +/- 5.2 mV and 25 +/- 5 mV, respectively). Ketamine also decreased the SD duration at half maximal amplitude from 34.9 +/- 12.4 s to 22.2 +/- 12 s (p < 0.05). 8-OH-DPAT attenuated the duration of the SD from 42 +/- 15.6 s to 21.2 +/- 10.6 s (p < 0.05, 100 microM). These data indicate that not only NMDA receptor blockade, but also activation of the 5-HT1A receptor attenuates the SD and may be beneficial in the reduction of ischemic injury following focal cerebral ischemia.
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PMID:Effects of ionotropic glutamate receptor blockade and 5-HT1A receptor activation on spreading depression in rat neocortical slices. 1057 86

Activation of NMDA receptors evokes sustained fictive locomotion in the isolated spinal cord of the sea lamprey Petromyzon marinus (P. marinus), but in the river lamprey Lampetra fluviatilis (L. fluviatilis) the ventral root activity is often irregular. A previous study showed that the number of 5-HT immunoreactive fibres, neurones and varicosities are much lower in the spinal cord of L. fluviatilis than in P. marinus. To further analyse the underlying mechanisms, the present study investigated the role of the 5-HT system in stabilising fictive locomotion. In P. marinus a blockade of 5-HT1A receptors by spiperone reversibly increased the frequency and the coefficient of variation. This implies that there is an endogenous release of 5-HT during fictive locomotion that is important for the generation of locomotor activity. In L. fluviatilis bath applied NMDA or D-glutamate evoked in most cases irregular activity. An addition of 5-HT (0.5-2 microM) rapidly stabilised the burst generation and led to a sustained fictive locomotion. In a split-bath configuration, NMDA administered to the rostral part of the spinal cord in P. marinus evoked fictive locomotion in both the rostral part and the first few segments of the caudal part. When spiperone was added to the caudal part, the burst activity changed into tonic activity within 10 min. Taken together, these results indicate that activity in the intrinsic 5-HT system in the lamprey spinal locomotor network contributes significantly to the rhythm generation. The quantitative differences with regard to the 5-HT plexus between P. marinus and L. fluviatilis may account for the observed discrepancy between the two species.
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PMID:The spinal 5-HT system contributes to the generation of fictive locomotion in lamprey. 1101 Oct 21

In the present study, we investigated whether the antagonist of 5-HT1A receptors, WAY 100135, was capable of modifying the psychostimulant and psychotomimetic effects of MK-801, a non-competitive antagonist of NMDA receptors. It was found that: 1) WAY 100135 (10 and 20 mg/kg, but not 1.25, 2.5, and 5 mg/kg) transiently, in a dose dependent manner, attenuated the locomotor stimulant effects of MK-801 (0.4 mg/kg). Given alone, WAY 100135 had no effect on the locomotor activity of rats; 2) WAY 100135 (1.25 and 2.5 mg/kg, but not 10 or 20 mg/kg), attenuated or abolished the disruptive effects of MK-801 on the sensorimotor gating measured in a prepulse-induced inhibition of the acoustic startle response paradigm. WAY 100135 in all tested doses had no effect on the sensorimotor gating or amplitude of the acoustic startle response; 3) WAY 100135 (1.25, 2.5 mg/kg, but not 5 mg/kg) attenuated the detrimental effects of MK-801 on working memory and selective attention, measured in a delayed alternation task. Again, given alone, WAY 100135 did not influence the behavior of rats in that experimental paradigm; and 4) MK-801 (0.4 mg/kg) had no effect on the 5-HT1A receptor mRNA level in rat hippocampus, measured 2 and 24 hours after MK-801 administration. These data indicate that 5-HT1A receptors might be involved in the psychotomimetic effects of non-competitive NMDA receptor antagonists. In addition, 5-HT1A serotonin receptor antagonists and partial agonists may have potential antipsychotic properties.
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PMID:WAY 100135, an antagonist of 5-HT1A serotonin receptors, attenuates psychotomimetic effects of MK-801. 1102 20


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