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 the novel antidepressant tianeptine on behaviours induced by the serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) and the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) were investigated. Tianeptine (10 mg/kg, i.p.) significantly attenuated wet dog shakes (WDS) induced by 5-HTP (75 mg/kg, i.p.; 30 min after carbidopa 25 mg/kg, i.p.). The effect was most marked when 5-HTP and tianeptine were given together. The main metabolite of tianeptine also attenuated WDS. Components of the 5-HT syndrome (i.e. reciprocal forepaw treading, hind limb abduction, flat body posture) induced by 8-OH-DPAT (0.5 mg/kg, s.c.) were unaffected by tianeptine and 5-HTP given both singly or together. However, tianeptine significantly reduced faecal pellet formation but not cage crossings resulting from 8-OH-DPAT administration. These cage crossings but not the associated faecal pellet formation were reduced by 5-HTP. This reduction was prevented by tianeptine. The increase of extracellular 5-HT in the frontal cortex following administration of 5-HTP was opposed and the concurrent increase of extracellular 5-hydroxyindoleacetic acid (5-HIAA) was enhanced by tianeptine. The above behavioural and neurochemical findings indicate that tianeptine opposes the increase of 5-HT at receptor sites due to 5-HTP administration.
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PMID:Behavioural and neurochemical evidence for the decrease of brain extracellular 5-HT by the antidepressant drug tianeptine. 769 70

1. RS-15385-197, a highly potent and selective alpha 2-adrenoceptor antagonist, was examined in a variety of in vitro and in vivo functional tests to assess the selectivity of its interaction with central noradrenergic neurones in the rat. 2. In hypothalamic slices, RS-15385-197 was potent in augmenting K(+)-evoked release of [3H]-noradrenaline, with an EC50 of 9 nM. Idazoxan and yohimbine showed 100 fold less activity. This was due to its antagonist action at presynaptic alpha 2-adrenoceptors, as RS-15385-197 (10 microM), did not directly release [3H]-noradrenaline from cortical slices unlike reserpine (10 microM), and did not inhibit noradrenaline re-uptake into cortical synaptosomes. 3. In vivo, RS-15385-197 (0.5 mg kg-1, p.o.) increased levels of 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the cerebral cortex without modifying levels of 5-hydroxyindoleacetic acid (5-HIAA). This dose, but not a lower dose (0.1 mg kg-1, p.o.) caused beta-adrenoceptor down-regulation in the cortex when administered once daily for 14 days whereas 5-HT2 receptor number was unaltered, indicating a selective effect on noradrenergic transmission. 4. Selective depletion of cortical 5-HT by administration of p-chlorophenylalanine (PCPA; 100 mg kg-1, i.p. for 14 days) or 5,7-dihydroxytryptamine (5,7-DHT; 150 micrograms i.c.v.) prevented the beta-adrenoceptor down-regulation caused by RS-15385-197, indicating that a tonic 5-hydroxytryptaminergic input was required for it to elicit beta-adrenoceptor down-regulation. It was not possible to prevent the loss of activity of RS-15385-197 in these 5-HT-depleted animals by co-administration with the 5-HT1A partial agonist, 8-hydroxy-n-dipropyl aminotetralin (8-OH-DPAT, 0.3 mg kg-1, i.p. twice daily for final 3 days).5. At a dose (1 mg kg-1, p.o.) which completely prevented the hypoactivity produced by clonidine(0.1 mgkg-1, p.o.), RS-15385-197 did not affect behavioural stereotypy induced by 8-OH-DPAT(0.3 mg kg-1, s.c.). Similarly, following chronic dosing with the racemate, RS-15385-196 (3 mg kg-1,p.o., once daily for 14 days), there was no effect on the behavioural and hypothermic response to 8-OH-DPAT (0.5 mg kg-1, s.c.). Therefore, RS-1 5385-197 was selective for central alpha2-adrenoceptors over 5-HT1A receptors in in vivo functional tests.6. Thus, RS-15385-197 was highly selective in interacting with central noradrenergic neurones in the rat in vitro and in vivo. It is therefore currently the agent of choice for investigations of the role of alpha 2-adrenoceptors in the CNS.
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PMID:Modulation of central noradrenergic function by RS-15385-197. 809 21

1. The behavioural effects of the 5-HT1B receptor agonists, RU 24969 and CGS 12066B, have been investigated in C57/B1/6 mice. 2. RU 24969 (1-30 mg kg-1) produced intense and prolonged hyperlocomotion and other behavioural changes. 3. CGS 12066B caused similar effects, but they were much less pronounced, inconsistent and transient irrespective of whether this drug was given i.p. (1-15 mg kg-1) or i.c.v. (0.2-40 micrograms). However, CGS 12066B (7.5 and 15 mg kg-1) caused a dose-related inhibition of RU 24969 (7.5 mg kg-1)-induced hyperlocomotion indicating that the former is a 5-HT1B partial agonist. 4. RU 24969 (7.5 mg kg-1 i.p.)-induced hyperlocomotion was inhibited by the (-)-, but not (+)-isomers of pindolol (4 mg kg-1) and propranolol (20 mg kg-1) but not by metoprolol (10 mg kg-1) or ICI 118,551 (5 mg kg-1), consistent with an involvement of 5-HT1A or 5-HT1B receptors. 5. The response was not altered by the selective 5-HT1A receptor antagonist, WAY 100135 (5 mg kg-1, s.c.), the 5-HT2A/5-HT2C receptor antagonist, ritanserin (0.1 mg kg-1), the selective 5-HT3 receptor antagonist, ondansetron (1 mg kg-1) or the non-selective 5-HT receptor antagonists methysergide (3 mg kg-1) and metergoline (3 mg kg-1). 6. Although spiroxatrine (0.1 mg kg-1) and ketanserin (1 mg kg-1) inhibited RU 24969-induced hyperlocomotion, these effects were probably due to antagonism of dopamine D2 receptors and alpha 1-adrenoceptors respectively. 7. Taken together, these results indicate that RU 24969-induced hyperlocomotion results specifically from activation of central 5-HTIB receptors.8. Lesioning of 5-HT neurones with 5,7-dihydroxytryptamine (75 microg, i.c.v.) or depletion with pchlorophenylalanine(200 mg kg-1, i.p. for 14 days) had no effect on RU 24969-induced hyperlocomotiondemonstrating that the 5-HTIB receptors involved are postsynaptic and that they do not show super sensitivity.9. The involvement of other monoamine neurotransmitter systems in RU 24969-induced hyperlocomotionwas also examined. The response was inhibited by the al-adrenoceptor antagonist, prazosin(1 mg kg-1), the dopamine DI receptor antagonist, SCH 23390 (0.05 mg kg-1) and the dopamine D2 receptor antagonist, BRL 34778 (0.03 mg kg-1), but not by the M2-adrenoceptor antagonist, idazoxan(1 mg kg-1). Lesioning noradrenergic neurones with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine(100 mg kg-1) markedly attenuated this behaviour. These results show that the hyperlocomotion is expressed via noradrenergic and dopaminergic neurones acting on alpha 1-adrenoceptors, DI and D2 receptors.10. RU 24969 decreased brain concentrations of 5-hydroxyindoleacetic acid whilst simultaneously increasing 5-HT, consistent with the reduction of 5-HT neuronal activity by activation of 5-HTlA and 5-HTIB autoreceptors. RU 24969 increased brain 3-methoxy-4-hydroxyphenylglycol, but not noradrenaline, concentrations which supports the involvement of noradrenergic neurones in the expression of hyperlocomotion. RU 24969 did not alter dopamine, dihydroxyphenylacetic acid or homovanillic acid concentrations in the nucleus accumbens suggesting that the dopaminergic neurones terminating there are not directly involved.
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PMID:Evidence that RU 24969-induced locomotor activity in C57/B1/6 mice is specifically mediated by the 5-HT1B receptor. 830 9

Exposure to HBO causes hypothermia, bradycardia, head weaving, resting tremor, piloerection, and straub tail in rats. These physiological and behavioral responses can also be evoked by selective activation of serotonin1A (5-HT1A) receptors. The purpose of the current study was to determine if hypothermia caused by HBO is due to increased activation of 5-HT1A receptors. The levels of brain biogenic amines were measured in brain regions of Sprague-Dawley (SD) rats exposed to HBO. Exposure to HBO caused an increase in the levels of 5-hydroxyindoleacetic acid (5-HIAA) in the striatum (92%, p < 0.05) and occipital-temporal cortex (116%, p < 0.05), but not in other brain regions. Exposure to HBO did not change the levels of tryptophan, serotonin (5-HT), other biogenic amines, or their metabolites. It is hypothesized that the Fawn Hood (FH) rat, which is reported to be resistant to hypothermia induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), has an abnormality of 5-HT1A receptor activity. Although the FH rat was more resistant to hypothermia induced by HBO than the SD rat, we were not able to confirm that this rat was resistant to hypothermia induced by 8-OH-DPAT. The 5-HT receptor antagonists, 1-(1H-Indol-4-yloxy)-3-[(1-methylethyl)amino]-2-propanol (Pindolol), 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190), and methysergide, did not block hypothermia induced by HBO in SD rats. A series of control experiments were used to confirm that the antagonists blocked hypothermia induced by serotonin agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypothermia induced by hyperbaric oxygen is not blocked by serotonin antagonists. 844 68

Selective central benzodiazepine agonists, such as clonazepam, are known to modify serotonin and 5-hydroxyindoleacetic content in the brain. In order to further study the effect of this benzodiazepine on serotonin turnover rate, rats received clonazepam, 10 mg/kg for 10 days, and the concentrations of serotonin and 5-hydroxyindoleacetic acid were determined in the hippocampus after inhibition of monoamineoxidase with pargyline. The results indicate a reduction in the turnover rate of the monoamine. In addition, the systemic administration of clonazepam produced a decrease in the Bmax of [3H]DPAT binding to 5-HT1A sites in the hippocampus. By contrast, this effect was not observed if clonazepam was delivered into the dorsal raphe nucleus by osmotic minipumps. The binding of [3H]paroxetine to 5-HT reuptake sites was increased by the treatment with clonazepam. The present observations indicate that clonazepam produces a reduction of serotonin turnover rate in the hippocampus of the rat concomitant with a down-regulation of 5-HT1A binding sites, probably by an effect at the forebrain projections. There is also an up-regulation of the serotonin transporter, which might contribute to a reduction in the synaptic availability of serotonin during clonazepam treatment.
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PMID:Serotonin turnover rate, [3H]paroxetine binding sites, and 5-HT1A receptors in the hippocampus of rats subchronically treated with clonazepam. 857 30

In the current study we examined the effects of coadministration of a serotonin 5-HT1A antagonist, (+-)-1-(1H-indol-4-yloxy)-3-(cyclohexylamino)-2-propanol maleate (LY 206130), and a dual 5-HT and norepinephrine (NE) uptake inhibitor, duloxetine, on extracellular levels of NE, 5-HT, dopamine (DA), 5-hydroxyindoleacetic acid, and 3,4-dihydroxyphenylacetic acid in rat hypothalamus microdialysates. LY 206130 (3.0 mg/kg, s.c.) alone significantly increased NE and DA levels by 60 and 34%, respectively, without affecting 5-HT levels. Duloxetine administration at 4.0 mg/kg, i.p. alone produced no significant changes in levels of 5-HT, NE, or DA. In contrast, when LY 206130 and duloxetine were coadministered at 3.0 mg/kg, s.c. and 4.0 mg/kg, i.p., respectively, 5-HT, NE, and DA levels increased to 5.7-, 4.8-, and threefold over their respective basal levels. These data demonstrate that antagonism of somatodendritic 5-HT1A autoreceptors and concomitant inhibition of 5-HT and NE uptake with duloxetine may promote synergistic increases in levels of extracellular 5-HT, NE, and DA in hypothalamus of conscious, freely moving rats.
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PMID:Antagonism of serotonin 5-HT1A receptors potentiates the increases in extracellular monoamines induced by duloxetine in rat hypothalamus. 859 29

In vivo microdialysis in guinea pig hypothalamus was used to study the effect of serotonin [5-hydroxytryptamine (5-HT)] subtype 1D autoreceptor blockade on the increase in extracellular 5-HT levels produced by a selective 5-HT reuptake inhibitor (SSRI). Administration of the selective 5-HT1D antagonist GR127935 at 0.3 mg/kg had no effect, but 5 mg/kg significantly increased extracellular levels of 5-HT and 5-hydroxyindoleacetic acid to 135% of basal values. Moreover, at these doses GR127935 significantly attenuated the decrease in extracellular 5-HT levels following local perfusion with the selective 5-HT1D agonist CP-135,807. The SSRI sertraline at 2 mg/kg increased 5-HT levels to 130% of basal levels. The combination of this low dose of sertraline with either dose of GR127935 resulted in a pronounced, long-lasting increases in 5-HT levels to 230% of basal values. These results indicate that the effects of an SSRI on terminal 5-HT are significantly enhanced by coadministration of a 5-HT1D antagonist and confirm that in addition to somatodendritic 5-HT1A autoreceptors, terminal 5-HT1D autoreceptors mitigate the effect of SSRIs on terminal 5-HT. As such, antagonists of the 5-HT1D autoreceptor could be useful as rapidly acting antidepressants and may shorten the onset of antidepressant action when combined with SSRIs.
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PMID:Combined administration of a 5-hydroxytryptamine (5-HT)1D antagonist and a 5-HT reuptake inhibitor synergistically increases 5-HT release in guinea pig hypothalamus in vivo. 920 42

1. The present study has examined the effect of (+)-WAY 100135, a selective antagonist of 5-HT1A receptors, and ketanserin, an antagonist of 5-HT2 receptors, on the urinary excretion of Na+, K+, dopamine, 5-hydroxytryptamine (5-HT) and their metabolites in rats treated with the selective type A monoamine oxidase (MAO-A) inhibitor, Ro 41-1049 (15 mg kg-1 day-1) in conditions of normal sodium (NS) and high sodium (HS; 1.0% NaCl in drinking water) intake. 2. Male Wistar rats were placed in metabolic cages and were given tap water (NS diet) in the first 4 days of the study and then challenged to a HS diet for another 7 days. Ro 41-1049 was given in drinking water only in the last 3 days of the HS diet, whereas (+)-WAY 100135 (5 and 10 mg kg-1 day-1, s.c.) or ketanserin (2 mg kg-1 day-1, s.c.) were administered in the last 4 days of the HS intake period. 3. Daily urinary excretion (in nmol kg-1 day-1) of dopamine (82 +/- 2), 3,4-dihydroxyphenylacetic acid (DOPAC; 198 +/- 9), homovanillic acid (HVA; 915 +/- 47), 5-HT (586 +/- 37) and 5-hydroxyindoleacetic acid (5-HIAA; 1035 +/- 64) in the HS intake period was similar or higher than that in NS diet (dopamine = 68 +/- 2, DOPAC = 197 +/- 4, HVA = 923 +/- 42, 5-HT = 539 +/- 132, 5-HIAA = 1286 +/- 95). The administration of Ro 41-1049 on 3 consecutive days reduced the urinary excretion of dopamine, DOPAC and HVA, respectively, by 35-51% (P < 0.05), 73-85% (P < 0.05) and 59-66% (P < 0.05); the urinary excretion of 5-HT increased 2 fold (P < 0.01) and the levels of 5-HIAA were reduced by 39-77% (P < 0.05). 4. During HS intake (7 days), daily urinary excretion of Na+ increased 5.5 fold (from 6.7 +/- 0.2 to 36.5 +/- 0.9 mmol kg-1 day-1), without changes in the urinary excretion of K+ (from 11.2 +/- 0.2 to 11.9 +/- 0.5 mmol kg-1 day-1) and urinary osmolality (from 1083.8 +/- 26.7 to 1117.7 +/- 24.1 mOsm kg-1 H2O). MAO-A inhibition during HS intake was found to produce a 47-68% decrease in Na+ excretion (from 39.1 +/- 0.7 to 15.1 +/- 2.5 mmol kg-1 day-1, n = 4; P < 0.02) and urine volume (from 160.4 +/- 3.3 to 43.8 +/- 9.0 ml kg-1 day-1, n = 4; P < 0.02) without changes in K+ (from 11.1 +/- 0.5 to 9.2 +/- 0.6 mmol kg-1 day-1, n = 4) and creatinine (from 29.1 +/- 2.3 to 28.4 +/- 2.1 mg kg-1 day-1) excretion; urine osmolality increased 2 fold (from 936.3 +/- 40.3 to 2210.7 +/- 157.4 mOsm kg-1 H2O, n = 4; P < 0.02). Administration of (+)-WAY 100135 (5 and 10 mg kg-1 day-1), but not of ketanserin (2 mg kg-1 day-1), was found to inhibit the antinatriuretic effect induced by Ro 41-1049 during HS intake. 5. It is suggested that MAO-A inhibition during HS intake leads to an increased availability of 5-HT in renal tissues, the effect of which is a decrease in the urinary excretion of Na+, involving the activation of tubular 5-HT1A receptors.
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PMID:Antagonistic actions of renal dopamine and 5-hydroxytryptamine: endogenous 5-hydroxytryptamine, 5-HT1A receptors and antinatriuresis during high sodium intake. 888 15

In in vitro receptor binding and synaptosomal uptake experiments the (+)-enantiomer of tramadol (CAS 148229-78-1) is specific for the mu-opioid receptor site and for the serotonin (5-HT) carrier, whereas the (-)-enantiomer (CAS 148229-79-2) has a higher affinity to the noradrenaline (NA) transporter. The antinociceptive active tramadol metabolite O-demethyltramadol (M1) shows a pronounced mu-selectivity. With respect to in vitro receptor binding experiments, the affinity of (+)-M1 to this opioid receptor subtype is more than two orders of magnitude higher than that of (+)-tramadol and approximately 1/10 that of morphine. Tramadol and M1 (and the enantiomers thereof) have no affinity to other receptor or uptake sites tested, e.g. 5-HT1A, 5-HT2, 5-HT3, NMDA (ligand: MK801), dopamine (DA)-D1, DA-D2, benzodiazepine, muscarine M1 and DA uptake (Ki > or = 2 x 10(-5) mol/l). Ex vivo neurotransmitter determinations show that tramadol (46.4 mg/kg i.p.) elevates the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid and enhances DA release in definite brain areas. The active enantiomer of the racemic tramadol is the (+)-enantiomer. (+)-Tramadol significantly enhances the turnover rate of DA. The enantioselective elevation of DOPAC by (+)-tramadol is antagonized by naloxone (2 x 5 mg/kg i.p.). Morphine (21.5 mg/kg i.p.) enhances the turnover of NA in definite brain areas. Neither the NA-specific uptake inhibition nisoxetine (31.6 mg/kg i.p.) nor tramadol (or its (+)- and (-)-enantiomers) have any influence on the NA turnover. Tramadol reduces the levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid. Morphine enhances, whereas tramadol reduces, 5-HT utilisation in the brain areas under assay. The 5-HT specific uptake inhibitor fluoxetine (20 mg/kg i.p.) shows the same influence on 5-HT turnover as tramadol. The results indicate that tramadol enhances DA turnover via an opioid mechanism. The interaction with the noradrenergic and serotonergic neurotransmission is clearly different from that of an opioid receptor agonist and closely resembles that of NA and 5-HT uptake inhibitors.
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PMID:Influence of tramadol on neurotransmitter systems of the rat brain. 895 60

Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels, tryptophan hydroxylase (TPH) activity, and 5-HT1A receptor binding were studied in brain areas of male mice after repeated experience of victories (winners) and defeats (losers) in daily male confrontations. A decrease in the TPH activity in midbrain and its decrease in hypothalamus were shown in winners in comparison with controls. The victory experiences were accompanied by a pronounced increase of Bmax of 5-HT1A receptors in the frontal cortex and decrease of Kd in the hypothalamus. Repeated defeats in social confrontations were accompanied by an increase in 5-HT level in the amygdala and increase of 5-HIAA/5-HT index in the hippocampus in comparison with controls. A decrease of Bmax in the hypothalamus and of Kd of 5-HT1A receptors both in the frontal cortex and hypothalamus was shown in losers as compared to controls. An increase in TPH activity under the influence of repeated defeats was shown in striatum and hypothalamus. The obtained evidence point to specific changes in serotonergic activity which characterize aggressive or submissive types of social behaviour, and unspecific changes which are similar in winners and losers and are likely to be induced by social stress.
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PMID:[The effect of the repeated experience of victories and defeats in social conflicts on the function of the brain serotoninergic system in male mice]. 905 61


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