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 modulatory role of serotonin (5-HT) on the acoustic startle reflex was studied using 5-HT receptor agonists and antagonists. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) (1,2 and 4 mg/kg, SC) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (1,2 and 4 mg/kg, IP), putative 5-HT1a receptor agonists, increased the magnitude of the startle reflex, while quipazine (5, 10 and 20 mg/kg, SC), an agonist with mixed 5-HT2 and 5-HT1b receptor activity, decreased startle responsiveness. Pretreatment of rats with ketanserin (1, 2 and 4 mg/kg, SC), a 5-HT2 receptor antagonist, had no significant effect on the activity of 8-OHDPAT, 5-MeODMT, or quipazine. Metergoline (0.25, 0.5, 1 and 2 mg/kg, SC), a mixed 5-HT1/5-HT2 receptor antagonist attenuated the augmentation of the reflex by 8-OHDPAT and 5-MeODMT and the suppression produced by quipazine. At the doses used, metergoline produced a non-dose-dependent increase in startle, while ketanserin had no effect. None of the agents specifically affected the ability of a prepulse stimulus to inhibit the acoustic startle response. These data suggest that 5-HT1a and 5-HT1b receptors play opposite roles in the modulation of the acoustic startle response and that 5-HT plays little, if any, role in the prepulse inhibition of the acoustic startle response.
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PMID:The role of 5HT1A receptors in the modulation of the acoustic startle reflex in rats. 252 58

The effect of different serotonin (5-HT) agonists and antagonists on the discriminative stimulus properties (cue) induced by 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OHDPAT), 1-(m-trifluoromethylphenyl)piperazine (TFMPP) and d-LSD (d-lysergic acid diethylamide) has been investigated. The 8-OHDPAT cue was mimicked by the 5-HT1A agonists ipsapirone, buspirone, gepirone and partially by 5-methoxy-N,N-dimethyltryptamine and d-LSD. 5-HT1B (TFMPP and RU 24969) and 5-HT2 agonists (DOM, DOI and quipazine) were ineffective and induced disruption of responding. The 8-OHDPAT cue was antagonized by spiroxatrine and partially by (-)-alprenolol, whereas selective antagonists of 5-HT2 (ketanserin and ritanserin), 5-HT3 (ICS 205-930), alpha 1-adrenergic (prazosin) and beta-adrenergic receptors (ICI 118.551) were ineffective. The TFMPP cue was mimicked by RU 24969 and partially by quipazine. Other compounds were ineffective. Only (-)-alprenolol antagonized the effect of TFMPP. The d-LSD cue was mimicked by DOM, DOI, quipazine, 5-methoxy-N,N-dimethyltryptamine and partially by ipsapirone, TFMPP and RU 24969. The 3 latter compounds and 5-HT1A agonists induced disruption of responding. The d-LSD cue was antagonized by ketanserin and ritanserin, but not by the other antagonists mentioned above. The specific inhibitor of 5-HT uptake citalopram was not able to substitute for any of the 3 agonists. It is concluded that the drug discrimination technique can be used to identify selective agonists and antagonists of 5-HT receptor subtypes. Compounds with mixed effects on 5-HT receptor subtypes can also be identified. These show additional effects on reaction time and often disrupt responding at higher dosages.
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PMID:Characterization of the discriminative stimulus properties induced by 5-HT1 and 5-HT2 agonists in rats. 252 50

Local application of the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the median raphe of rats caused locomotor stimulation. In contrast, dorsal raphe application of the compound induced flat body posture, which was discontinuous and not dose-dependent, and therefore distinct from that characteristic for postsynaptic 5-HT receptor-mediated behaviour. Injection of 8-OH-DPAT into the dorsal raphe or median raphe caused neither forepaw treading nor head-weaving; stiff tail and sniffing occurred inconsistently. By activating somatodendritic 5-HT1A autoreceptors in the median raphe, 8-OH-DPAT may disinhibit locomotor-enforcing neural pathways that receive 5-HT afferents from this nucleus. The data suggest that median raphe and dorsal raphe 5-HT neurons have different roles in motor control.
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PMID:Median raphe, but not dorsal raphe, application of the 5-HT1A agonist 8-OH-DPAT stimulates rat motor activity. 252 61

The effects of ethanol on serotonin (5-hydroxytryptamine, 5-HT) receptor binding in rat and mouse brain were determined under in vitro conditions and in mouse brain following seven days of ethanol ingestion. 5-HT1A receptor characteristics were measured utilizing the agonist [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([ 3H]DPAT), and 5HT2 receptor-binding studies utilized the antagonist [3H]ketanserin. At the highest concentration of ethanol tested in vitro (680 mM), there was only 25% inhibition of [3H]DPAT binding in rat and mouse brain and 14% inhibition of [3H]ketanserin binding in rat brain. Effects of an anesthetic concentration of ethanol (100 mM) on agonist binding in the presence and absence of the guanine nucleotide GTP were also evaluated in vitro in mouse brain. In no case did ethanol (100 mM) significantly affect 5-HT1A or 5-HT2 receptor-binding characteristics. When 5-HT receptor characteristics were measured after mice consumed ethanol for seven days, there was no change in either 5-HT1A or 5-HT2 receptor-binding properties in any of the brain areas examined.
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PMID:Ethanol does not affect serotonin receptor binding in rodent brain. 252 20

The involvement of serotonin (5-HT) in modulating the acoustic startle response (ASR) is well established in adult rats, but 5-HT involvement during the preweaning period, when 5-HT neurons undergo extensive development, has not previously been described. Three 5-HT receptor subtypes are reported to modulate the ASR in adult rats: 5-HT1A and 5-HT2 receptor agonists facilitate the ASR, whereas 5-HT1B agonists decrease the response. In the present study, the effects of 5-HT agonists and generalized 5-HT depletion on the ASR were studied in preweanling animals, using independent groups of Long-Evans rats tested on postnatal day (PND) 13, 17 and 21. 8-Hydroxy-2-(di-n-propylamino) tetralin (8OHDPAT, 62-1000 micrograms/kg), a 5-HT1A receptor agonist, and 5-methoxy-N,N-dimethyl tryptamine (MeODMT, 2-4 mg/kg), a nonselective 5-HT agonist, had no effect on PND 13 and then increased the ASR on PND 17 and 21. The 5-HT2 receptor antagonists cyproheptadine (5 mg/kg) and ketanserin (5 mg/kg) blocked the effect of MeODMT at both ages, providing some evidence that MeODMT increased the ASR through 5-HT2 receptors. 1-(m-Chlorophenyl) piperazine (mCPP, 1-5 mg/kg), a 5-HT1B agonist, had no effect on ASR amplitude on PND 13 or 17 and then produced a dose-related decrease in the response on PND 21. Generalized depletion of 5-HT by 80-90% in whole-brain and spinal cord, using p-chlorophenylalanine (PCPA, 300 mg/kg 24 hr prior to testing), did not alter ASR amplitude at any age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonergic modulation of the acoustic startle response in rats during preweaning development. 253 May 91

There is growing evidence that the serotonergic (5-HT) system is involved in the pathogenesis and treatment of major depression. The 5-HT receptor subtype involved in the enhancing effect of antidepressant treatments, however, has not been identified. The present study was undertaken to quantify 5-HT1A sites in the rat brain by autoradiography and membrane binding, using the selective ligand [3H]8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT), following long-term antidepressant treatment. Following a 21-day treatment with amitriptyline (10 mg/kg/day), there was a significant increase of [3H]8-OH-DPAT binding measured by autoradiography in the dorsal hippocampus, but there was no change in the nucleus raphe dorsalis; whole brain membrane binding revealed an increase in the number of binding sites, with no change in the affinity for [3H]8-OH-DPAT. Conversely, fluoxetine (10 mg/kg/day), a selective blocker of 5-HT reuptake, and gepirone (10 mg/kg/day), a 5-HT1A agonist, both administered for 21 days, significantly reduced [3H]8-OH-DPAT binding measured by autoradiography in the nucleus raphe dorsalis without altering hippocampal binding sites. The control active treatment with diazepam (2 mg/kg/day) did not alter [3H]8-OH-DPAT binding in the hippocampus or in the nucleus raphe dorsalis. All groups were compared to a 21-day vehicle-treated control group. These results are fully consistent with previous electrophysiological and behavioral studies and suggest that alterations of 5-HT1A receptors might underlie the enhancement of 5-HT neurotransmission by antidepressant treatments.
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PMID:Autoradiographic quantification of serotonin1A receptors in rat brain following antidepressant drug treatment. 253 23

1-(3-Trifluoromethylphenyl)piperazine (TFMPP), a serotonin1 (5-HT1) receptor agonist, injected i.p. in doses of 0.1 and 0.6 mg/kg, did not modify the immobility time of rats in the forced swimming test but significantly antagonized the effect of a 7 days treatment with 10 mg/kg per day desipramine (DMI). A similar effect was found on infusing 1 and 5 micrograms/microliters TFMPP bilaterally into the ventral tegmental area (VTA). Infusion of 5 micrograms/microliters TFMPP into the nucleus accumbens or into the globus pallidus did not modify the effect of DMI. The effect of 5 micrograms TFMPP infused into the VTA was prevented by the i.p. administration of 5 mg/kg metergoline, a non-selective serotonin receptor antagonist. Infusion of 5 micrograms/microliters 8-hydroxy-2-(di-n-propylamino)tetralin, a specific 5-HT1A receptor agonist, into the VTA did not modify the effect of DMI. Besides acting as a 5-HT1B receptor agonist, TFMPP may also act on other 5-HT receptor types, but available evidence suggests that its former action is more important. It thus appears that 5-HT1 receptors in the VTA, presumably of the 5-HT1B type, act by preventing the anti-immobility effect of DMI. The role of VTA dopamine and non-dopamine cells in the effect of TFMPP is discussed.
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PMID:1-(3-Trifluoromethylphenyl) piperazine (TFMPP) in the ventral tegmental area reduces the effect of desipramine in the forced swimming test in rats: possible role of serotonin receptors. 253 79

The characteristics of high affinity [3H]5-HT (5-hydroxytryptamine) binding to non 5-HT1A non 5-HT1C sites were examined in crude membranes prepared from different regions of guinea-pig and pigeon brains. The coupling of these sites to adenylate cyclase was examined, and its pharmacological profile investigated. In the presence of 100 nmol/l 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) and 100 nmol/l mesulergine, [3H]5-HT labelled with nanomolar affinity an apparently homogeneous population of recognition sites in guinea-pig and pigeon brain membranes. The rank order of affinities of agonists and antagonists (5-CT (5-carboxamidotryptamine) greater than 5-HT greater than RU 24969 (5-methoxy-3-(1,2,3,6-tetrahydro-4- pyridinyl)-1H indole succinate) greater than yohimbine greater than or equal to rauwolscine greater than DP-5-CT (N,N dipropyl-5-carboxamidotryptamine) greater than or equal to mianserin greater than 8-OH-DPAT greater than mesulergine greater than SDZ 21-009 ((+/-)-4(3-tert-butyl-amino-2-hydroxypropoxy)-indol-2 carbonic acid isopropyl ester) greater than (-)propranolol), as well as their individual pKD values, were very similar to those at porcine caudate 5-HT1D sites and clearly different from those at rat cortex 5-HT1B sites. In the substantia nigra of the guinea-pig the 5-HT receptor-mediated inhibition of forskolin-stimulated adenylate cyclase had a pharmacological profile fully comparable to that of 5-HT1D binding sites (5-CT greater than 5-HT greater than yohimbine greater than RU 24969 greater than 8-OH-DPAT greater than SDZ 21-009 = isamoltane greater than (-)pindolol greater than (-)propranolol).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5-HT1D receptors in guinea-pig and pigeon brain. Radioligand binding and biochemical studies. 253 24

In anaesthetised rats bilateral microinjection of 2 nmol 5-HT or the agonists 5-carboxyamidotryptamine (5-CT), 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) into nucleus paragigantocellularis lateralis produced a fall in blood pressure and heart rate, an increase in hindlimb vascular conductance but no significant change in renal conductance. In contrast, alpha-methyl-5-HT injected into the same region had no such effects. It is suggested that these cardiovascular effects are mediated by activation of 5-HT1A receptors. The possibility that there may be differences between species with respect to central 5-HT receptor-mediated cardiovascular effects is also discussed.
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PMID:Systemic and regional haemodynamic responses to microinjection of 5-HT agonists in the rostral ventrolateral medulla in the rat. 253 33

Intracellular recordings were made from neurons of rabbit vesical pelvic (parasympathetic) ganglia (VPG). Application of 5-hydroxytryptamine (5-HT, 0.3-30 microM) produced an initial depression followed by a long-lasting facilitation of the fast excitatory postsynaptic potential (e.p.s.p.) evoked by stimulation of the pelvic preganglionic nerve. The facilitation of nicotinic transmission lasted for 30-120 min, even when 5-HT was removed from the superfusing solution. 5-HT (0.3-30 microM) did not change the depolarization induced by a direct application of acetylcholine (ACh) to the VPG neurons pretreated with 1 microM atropine. 5-HT also caused an initial depression followed by an increase in the quantal content of the fast e.p.s.p. It is, therefore, suggested that diphasic effect of 5-HT on the nicotinic transmission is due mainly to a modulation of the ACh-release from presynaptic nerve terminals. Methysergide (5 microM), mianserin (5-30 microM) and ICS 205-930 (100-300 nM) did not antagonize the presynaptic actions of 5-HT on the nicotinic transmission, suggesting that the presynaptic 5-HT receptor may belong to a class of 5-HT1 subtypes. Spiperone (1 microM), a selective 5-HT1A antagonist, blocked the 5-HT-induced inhibition of the fast e.p.s.p. Under the effect of spiperone, the facilitation appeared soon after application of 5-HT. The facilitation of the fast e.p.s.p. may be mediated through a 5-HT1B or 5-HT1C subtype. Lowering temperature of the external solution eliminated the 5-HT-induced facilitation of the nicotinic transmission. Forskolin produced a presynaptic facilitation of the fast e.p.s.p., without producing an initial depression. 3-Isobutyl-1-methylxanthine (10 microM) potentiated the facilitatory action of 5-HT. Bath-application of dibutyryl cyclic adenosine monophosphate (cAMP) (1-6 mM) and 8-bromo-cyclic AMP (2-5 mM) mimicked the effect of 5-HT in producing the facilitation of the fast e.p.s.p.s. All data presented are consistent with the hypothesis that 5-HT, acting on presynaptic 5-HT1 receptors, causes a facilitation in the release of ACh from preganglionic nerve terminals possibly mediated through an activation of adenylate cyclase.
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PMID:5-Hydroxytryptamine produces presynaptic facilitation of cholinergic transmission in rabbit parasympathetic ganglia. 254 88


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