Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sucrose gap recordings from the ventral roots of isolated, hemisected frog spinal cords were used to evaluate the effects of high concentrations of serotonin (5-HT) and alpha-methyl-5-HT (alpha-Me-5-HT) on the changes in motoneuron potential produced by dorsal root stimulation and by excitatory amino acids and agonists. Bath application of 5-HT in concentrations of 10 microM or greater produced a concentration-dependent motoneuron depolarization. Polysynaptic ventral root potentials evoked by dorsal root stimuli were reduced in both amplitude and area by 5-HT or alpha-Me-5-HT (both 100 microM). This may result from a reduction of the postsynaptic sensitivity of motoneurons to excitatory amino acid transmitters because 5-HT significantly depressed motoneuron depolarizations produced by addition of L-glutamate and L-aspartate to the superfusate. Similarly, 5-HT reduced depolarizations produced by the excitatory amino acid agonists N-methyl-D-aspartate (NMDA), quisqualate, alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), and kainate. alpha-Me-5-HT reduced NMDA depolarizations. Tetrodotoxin (TTX) did not affect the ability of 5-HT to attenuate NMDA or kainate depolarizations, but did eliminate the 5-HT-induced attenuation of quisqualate and AMPA depolarizations. The glycine receptor site associated with the NMDA receptor did not appear to be affected by 5-HT because saturation of the site by excess glycine did not alter the 5-HT-induced depression of NMDA responses. The 5-HT1C/2 antagonist ketanserin and the 5-HT1A/2 antagonist spiperone significantly attenuated the 5-HT-induced depression of NMDA-depolarizations.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Activation of 5-HT1C/2 receptors depresses polysynaptic reflexes and excitatory amino acid-induced motoneuron responses in frog spinal cord. 132 Apr 45

The non-competitive NMDA receptor antagonist, MK-801 (dizocilpine), induces in rats a characteristic behavioural syndrome with ataxia, stereotypies and hyperlocomotion. At least part of this behavioural syndrome is thought to be related to interactions between glutamatergic and dopaminergic neurotransmission. Based on recent biochemical evidence that serotonin (5-HT) might also be involved in the effects of MK-801 several 5-HT receptor ligands were tested for effects on MK-801-induced behaviours. The 5-HT1A receptor ligands, ipsapirone and NAN-190, which are known to display antagonist-like properties in functional models of postsynaptic 5-HT1A receptor activity attenuated or blocked the hyperlocomotion and head weaving observed after administration of MK-801, whereas the 5-HT2 receptor antagonist, ritanserin, was ineffective in this respect. The dopamine receptor antagonist, haloperidol, and the alpha 1-adrenoceptor antagonist, prazosin, also attenuated behaviours induced by MK-801. In contrast to its effects on stereotypies induced by MK-801, ipsapirone potentiated rather than attenuated the stereotyped behaviour induced by the dopamine receptor agonist, apomorphine, indicating that antagonism of MK-801-induced stereotypies by ipsapirone may not be related to the dopaminergic system. The data indicate that, in addition to catecholaminergic systems, serotonergic neurotransmission is significantly involved in the mechanisms by which MK-801 alters behaviour in rats.
 ...
PMID:The behavioural effects of MK-801 in rats: involvement of dopaminergic, serotonergic and noradrenergic systems. 135 90

Experimental lesions followed by binding of [3H]4-trans-2-carboxy-5,7-dichloro-4-phenylamino-carbonylamino-1,2 ,3,4- tetrahydroquinoline ([3H]L-689,560, a novel ligand that binds to the glycine modulatory site), [3H]glycine and [3H]glutamate (N-methyl-D-aspartate (NMDA) sensitive) to cryostat sections and quantitative autoradiography were used to investigate the cellular localization of the NMDA receptor complex in the neocortex of the rat. The lesions were produced by intrastriatal injections of either volkensin (2 and 6 ng) or ricin (10 ng): both are suicide transport agents but only the former is retrogradely transported in the CNS. The binding of [3H]L-689,560 was significantly reduced in rats receiving 2 or 6 ng volkensin in deep cortical layers of Fr1/Fr2 ipsilateral to the striatal lesion. Similar reductions were also seen in [3H]glycine and [3H]glutamate binding, but only in rats receiving 6 ng volkensin. Quantitative histological analysis had previously revealed a loss of large infragranular pyramidal neurones with sparing of both interneurones and supragranular pyramidal neurones. There were no significant reductions in binding of any ligand in the superficial layers. In cortical areas Par1/Par2, [3H]L-689,560 was also significantly reduced in deep layers but only in rats receiving 6 ng volkensin. Binding was also reduced in the superficial layers by contrast to Fr1/Fr2. [3H]Glycine and [3H]glutamate binding were unaffected in this area. Binding of [3H]L-689,560 was unaffected in any area following intrastriatal ricin injection. The present study indicates that the NMDA receptor complex is present on pyramidal cells forming the corticofugal pathways. This is discussed in terms of the 5-HT1A receptor which is enriched on these cells.
 ...
PMID:NMDA receptors assessed by autoradiography with [3H]L-689,560 are present but not enriched on corticofugal-projecting pyramidal neurones. 136 17

The novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849) was found to produce a phencyclidine (PCP)-like behavioral syndrome (ataxia, locomotion, stereotypies) in amygdala-kindled rats, whereas the amphetamine-like behavioral alterations of the syndrome (locomotion, stereotypies) were only infrequently seen in nonkindled rats. In dose-response experiments in kindled and nonkindled rats, behavioral effects were scored using a ranked intensity scale, and the behaviors and behavioural scores determined after CGP 37849 were compared with those determined after i.p. administration of the noncompetitive NMDA receptor antagonist dizocilpine maleate (MK-801). In kindled rats, 20 mg/kg of CGP 37849 produced about the same scores for hyperlocomotion and head weaving as 0.1 mg/kg of MK-801. Kindled rats exhibited higher behavioral scores than nonkindled rats, especially in the case of CGP 37849. The behavioral effects produced by CGP 37849 in kindled rats were almost indistinguishable from the PCP-like behavioral effects induced by MK-801, indicating that CGP 37849 indeed produces a PCP-like pattern of behavior in kindled rats. Hyperlocomotion and head weaving induced by CGP 37849 in kindled rats could be attenuated or totally prevented by pretreatment with ipsapirone, a partial agonist/antagonist at postsynaptic 5-hydroxytryptamine (5-HT) receptors of the 5-HT1A subtype. Furthermore, these behavioural effects were attenuated or blocked by the dopamine antagonist haloperidol and the alpha-1 adrenoceptor antagonist, prazosin. The data demonstrate that kindling induces a hypersensitivity to PCP-like behavioral effects of competitive and noncompetitive NMDA receptor antagonists, which could relate to the recent finding of increased function of NMDA receptors following kindling.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The novel competitive N-methyl-D-aspartate (NMDA) antagonist CGP 37849 preferentially induces phencyclidine-like behavioral effects in kindled rats: attenuation by manipulation of dopamine, alpha-1 and serotonin1A receptors. 167 88

Pre-weaning rat pups emit ultrasonic vocalizations when removed from the litter. These 'separation-induced vocalizations' (SIV) are suppressed by classical benzodiazepine anxiolytics and by non-benzodiazepine anxiolytics which lack muscle relaxant and sedative properties. The present study used the SIV model to assess potential anxiolytic properties of compounds which target different sites associated with the NMDA receptor complex. Comparison was made to drugs which affect benzodiazepine or serotonin (5-HT) receptors. Muscle relaxant potential was assessed using 'TIP' (time on an inclined plane), the amount of time a pup was able to retain its position on a steeply inclined surface. Mephenesin, a centrally acting muscle relaxant, significantly suppressed TIP but not SIV. The benzodiazepine agonist diazepam suppressed both SIV and TIP, whereas the 5-HT1A partial agonists, buspirone and MDL 73,005EF, suppressed SIV without affecting TIP. The 5-HT2 antagonist MDL 11,939 suppressed TIP but not SIV, whereas neither measure was affected by the 5-HT3 antagonist MDL 73,147EF. SIV was suppressed by NMDA antagonists including those acting at the glutamate recognition site (D,L-amino-phosphonovaleric acid (AP5) and MDL 100,453) or at the ion channel (MK-801), or by the strychnine-insensitive glycine antagonist 5,7-dichlorokynurenic acid (5,7-DCKA). TIP was suppressed even more potently by AP5, MDL 100,453 and MK-801, whereas 5,7-DCKA was inactive on this measure. Thus, antagonists acting at different sites present on the glutamate recognition site exhibit potential anxiolytic activity, but the glycine antagonist was unusual in its lack of prominent muscle relaxant side effects.
 ...
PMID:NMDA receptor complex antagonists have potential anxiolytic effects as measured with separation-induced ultrasonic vocalizations. 167 93

In acutely isolated spinal dorsal horn neurons of the rat, effects of serotonin (5-hydroxytryptamine, 5-HT) on inward current induced by excitatory amino acids were studied under whole-cell voltage-clamp condition. 5-HT suppressed the response to N-methyl-D-aspartate (NMDA), but not the response to kainate or quisqualate. This inhibitory effect of 5-HT on NMDA response was present at 5-HT concentrations as low as 10(-15) M. Although the 5-HT effect exhibited similar pharmacology to the 5-HT1A-type receptors, it was not mimicked by increasing intracellular concentration of adenosine 3',5'-cyclic monophosphate that is the common second messenger for 5-HT1A receptors in the mammalian central nervous system. Glycine strongly antagonized this inhibitory effect of 5-HT, and 5-HT reduced opening of NMDA-gated single channels recorded from the outside-out membrane patch. These lines of evidence are consistent with a possibility that 5-HT might directly modulate the NMDA receptor-ion channel complex, either by interacting with the regulatory site(s) or by acting on a distinct site.
 ...
PMID:Serotonin suppresses N-methyl-D-aspartate responses in acutely isolated spinal dorsal horn neurons of the rat. 214 17

We examined the effects of manipulating 5-HT1A receptors on the performance of a passive avoidance task in rats. Firstly, we studied the effect of racemic 8-OH-DPAT and compared it to the pure enantiomers (subcutaneous injection, s.c.). Secondly, we investigated the effect (s.c.) of the selective 5-HT1A receptor antagonist (S)-UH-301 [(S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin] both alone and on 8-OH-DPAT-induced disruption of acquisition. Thirdly, we examined whether tolerance occurs to the effects of 8-OH-DPAT on passive avoidance acquisition. Finally, we examined the effects (s.c.) of the selective NMDA receptor antagonist dizocilpine, (+)-MK-801[(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohe pten-5, 10-imine], on this tolerance development. Different doses of racemic 8-OH-DPAT were injected 10 min before rats were exposed to the acquisition phase of a step through passive avoidance response. When tested for retention 24 h later, 8-OH-DPAT-pretreated rats failed to exhibit any avoidance. R(+) and S(-)-8-OH-DPAT were also active with the R(+)-isomer being more active than the S(-)-isomer. The 5-HT1A antagonist (S)-UH-301 [(S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin] was without effect on avoidance performance but antagonized the effect of 8-OH-DPAT. In a further experiment, rats were pretreated with racemic 8-OH-DPAT (0.3 mg/kg). Twenty four hours later, they received a challenge dose of 8-OH-DPAT and exposed to the acquisition phase of the avoidance response. When tested 24 hr later for retention, 8-OH-DPAT challenged rats failed to show any indication of an avoidance response.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Development of tolerance to 8-OH-DPAT induced blockade of acquisition of a passive avoidance response. 784 47

The amygdala (AM) and the periaqueductal gray (PAG) represent the rostral and the caudal pole, respectively, of a longitudinally organized neural system, that is responsible for the integration of behavioral and physiological manifestations of defensive reactions against innate and learned threats. Microinjection of benzodiazepine (BZD) anxiolytics, GABAA receptor agonists or 5-HT receptor antagonists into the AM has anxiolytic effects in conflict tests and other models of conditioned fear, while similar administration of 5-HT or of a 5-HT1A receptor agonist has anxiogenic effects. On the other hand, in the test of electrical stimulation of the PAG, microinjection of 5-HT, 5-HT mimetics, or of drugs that enhance the action of endogenous 5-HT into the same brain area has an antiaversive effect, like BZD and GABAA agonists. Furthermore, microinjection of midazolam, of the NMDA receptor antagonist AP-7, or of the 5-HT1A/1B receptor blocker propranolol increased the exploration of the open arms of the elevated plus-maze, having therefore an anxiolytic effect. These results point to an inhibitory role of the GABA-BZD system in both the AM and the PAG. In contrast, 5-HT seemingly enhances conditioned fear in the AM, while inhibiting unconditioned fear in the PAG. Thus, 5-HT2/1C antagonists reportedly release punished behavior when injected into the AM, whereas they antagonized the antiaversive effect of 5-HT, zimelidine and 5-HT1A/1B receptor blockers in the PAG. Since reported clinical studies revealed that one of such compounds, ritanserin, relieves generalized anxiety but tends to aggravate panic disorder, a relationship may be established between the AM and anxiety and the PAG and panic.
 ...
PMID:Role of the amygdala and periaqueductal gray in anxiety and panic. 813 40

We have recently shown that the stereotyped behaviour induced by the uncompetitive NMDA receptor antagonist dizocilpine (MK-801) can be attenuated or blocked by partial agonists at 5-HT receptors of the 5HT1A subtype, indicating that 5-HT (5-hydroxytryptamine, serotonin) is involved in the stereotyped behaviour produced by dizocilpine. In the present experiment, a selective, silent 5-HT1A receptor antagonist, (+)-WAY 100135 (N-tert-butyl 3-4(2-methoxyphenyl) piperazin 1-yl-2-phenylpropanamide dihydrochloride), was used to further study the role of 5-HT activation in dizocilpine-induced behaviours. At a dose of 10 mg/kg, (+)-WAY 100135 significantly reduced the intensity of head weaving induced by dizocilpine, but this effect was lost by increasing the dose to 20 mg/kg. At this higher dose, (+)-WAY 100135 induced marked but short-lasting increases in skeletal muscle tone and hindlimb abduction, resembling components of the '5-HT behavioural syndrome', which would explain its biphasic effects on dizocilpine induced behaviours. The data substantiate that, in addition to the well known activation of dopaminergic transmission, activation of the 5-HT system might be involved in the behavioural effects of NMDA receptor antagonists such as dizocilpine.
 ...
PMID:Effects of the novel 5-HT1A receptor antagonist, (+)-WAY 100135, on stereotyped behaviour induced by the NMDA receptor antagonist dizocilpine in rats. 822 42

The mechanisms of the antinociceptive effect of desipramine (DMI) are only partly known. It is generally accepted that excitatory amino acids act as neurotransmitters in primary nociceptive fibres and recent in vitro studies have shown an interaction between tricyclic antidepressants and the N-methyl-D-aspartic acid (NMDA) receptor complex. In this study, the modulatory effect of DMI on the biting and scratching behaviour induced by intrathecal (i.th.) administration of NMDA (0.25 nmol) was investigated. Desipramine was administered acutely, either intrathecally (0.7-35 micrograms) or intraperitoneally (i.p., 10 mg/kg), or chronically in the drinking water (0.15 g/l) for 3 weeks. The NMDA-induced behaviour was significantly reduced both after acute and chronic administration of DMI. Several studies have shown a functional upregulation of the 5-HT1A receptor after chronic treatment with DMI. The activation of this receptor using the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), leads to a reduction in NMDA-induced behaviour. Using the 5-HT1A antagonist NAN-190 (10 micrograms, i.th.), the effect of chronic administration of DMI on the NMDA-induced behaviour was reversed. However, NAN-190 also increased NMDA-induced behaviour in the control group, suggesting that a tonic inhibition of this behaviour, mediated by the 5-HT1A receptor, may exist. These findings indicate that DMI may reduce glutaminergic transmission at the spinal NMDA receptor. As this receptor is central in spinal nociceptive transmission, this could be one mechanism for the antinociceptive effect of DMI.
 ...
PMID:Reduction of NMDA-induced behaviour after acute and chronic administration of desipramine in mice. 833 22


1 2 3 4 5 6 Next >>