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)

Various models of rodent agonistic behaviour are described, which differentiate between offensive and defensive/flight models. Particular attention is given to one male and one female paradigm for offensive aggression, viz. resident-intruder or territorial (RI) and maternal aggression (MA). After an overview of the serotonin (5-HT) system in the CNS, a description is given of the ligands available. Subsequently the effects of various drugs affecting serotonergic transmission in the RI- and MA-paradigms are described. The 5-HT1A agonists buspirone, ipsapirone and 8-OH-DPAT decreased aggression in RI and MA, but simultaneously led to a marked decrease in social interest and activity, indicative of a non-specific anti-aggressive profile. Non-selective 5-HT1 agonists, such as RU 24969, eltoprazine (DU 28853), and TFMPP reduced aggression quite specific and did not decrease social interest or exploration, but sometimes even increased these behaviours. In RI and MA the behavioural effects of these drugs were roughly similar. In contrast, MA was more sensitive to the treatment with the 5-HT reuptake blocker fluvoxamine, which blocked RI aggression only non-specifically at the highest dose. DOI, a 5-HT2 and 5-HT1C agonist, decreased aggressive behaviour and increased inactivity, without affecting social interest and exploration in RI as well as MA. This was, however, accompanied by 'wet dog shaking', characteristic of 5-HT2-receptor stimulation. The non-specific 5-HT agonist (and 5-HT3 antagonist) quipazine also induced 'wet dog shaking' at doses which suppressed aggression, social interest and exploration but increased inactive behaviours (sitting and lying). The discussion attempts to delineate a role for 5-HT receptor subtype involvement in the modulation of aggression, with the restrictions we clearly face with regard to the lack of specific serotonergic agonists and antagonists for certain receptor subtypes. By and large, male and female rats react similarly to treatment with serotonergic drugs stressing the consistent role of 5-HT in different forms of aggression.
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PMID:Rodent models of aggressive behavior and serotonergic drugs. 151 29

Synaptosomes prepared from freshly obtained human cerebral cortex and labeled with [3H]choline have been used to investigate the modulation of [3H]acetylcholine ([3H]ACh) release by 5-hydroxytryptamine (5-HT). The Ca(2+)-dependent release of [3H]-ACh occurring when synaptosomes were exposed in superfusion to 15 mM KCl was inhibited by 5-HT (0.01-1 microM) in a concentration-dependent manner. The effect of 5-HT was mimicked by 1-phenylbiguanide, a 5-HT3 receptor agonist, but not by 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT1A receptor agonist. The 5-HT3 receptor antagonists tropisetron and ondansetron blocked the effect of 5-HT, whereas spiperone and ketanserin were ineffective. It is suggested that cholinergic axon terminals in the human cerebral cortex possess 5-HT receptors that mediate inhibition of ACh release and appear to belong to the 5-HT3 type.
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PMID:5-Hydroxytryptamine3 receptors sited on cholinergic axon terminals of human cerebral cortex mediate inhibition of acetylcholine release. 153 19

This study was designed to determine the subtypes of 5-HT receptors present in bovine large coronary arteries and to characterize the response mediated by each subtype of receptor. Concentration-response relationships for 8-hydroxy-2-(di-n-propylamino)-tetralin (5-HT1A agonist) (0.3-100 microM), CGS-12066B maleate (5-HT1B agonist) (0.01-30 microM), alpha-methylserotonin maleate (5-HT2 agonist) (0.01-30 microM), 1-(m-chlorophenyl)-biguanide (5-HT3 agonist) (0.1-100 microM) and serotonin (0.1-300 microM) were studied in vitro using 2-mm segments of bovine proximal left anterior descending coronary artery. Each segmental ring was mounted in a 70-ml tissue bath for the measurement of isometric tension. 8-Hydroxy-2-(di-n-propylamino)-tetralin (10-100 microM), alpha-methylserotonin maleate (0.01-30 microM) and serotonin (0.1-300 microM) induced endothelium-independent contraction, whereas CGS-12066B maleate and 1-(m-chlorophenyl)-biguanide had no effect in this species. Contractions induced by 8-hydroxy-2-(di-n-propylamino)-tetralin or alpha-methylserotonin maleate were attenuated by pretreatment with S(-)propranolol (2.6 microM), a relatively selective 5-HT1A and 5-HT1B receptor antagonist, and ketanserin (0.3 microM), a selective 5-HT2 receptor antagonist, respectively. Pretreatment with S(-)propranolol or ketanserin also attenuated serotonin-induced contraction, demonstrating that serotonin mediates contraction through both 5-HT1A and 5-HT2 receptors in bovine large coronary arteries.
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PMID:Characterization of 5-hydroxytryptamine receptors in bovine coronary arteries. 153 67

In this study, we have investigated serotonin hyperalgesia employing the mechanical paw withdrawal nociceptive threshold test in the rat. Intradermally injected serotonin was found to produce a dose-dependent hyperalgesia that was not attenuated by procedures which eliminate the known indirect mechanisms of hyperalgesia such as sympathectomy, polymorphonuclear leukocyte depletion or cyclooxygenase inhibition. In addition, the latency to onset of serotonin hyperalgesia is extremely short, with maximal hyperalgesia observed in less than 1 min, a similar temporal onset to direct-acting hyperalgesic agents such as prostaglandin E2. The results suggest, therefore, that the hyperalgesic effects of serotonin in our animal model are exerted by direct action on primary afferent neurons. Only the intradermal injection of selective serotonin (5-hydroxytryptamine; 5-HT) agonists for the 1A receptor subset (5-HT1A), (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthaline hydrobromide and N,N-dipropyl-5-carboxamido-tryptamine maleate, produced dose-dependent hyperalgesia. No hyperalgesia was seen after 5-HT1B, CGS-12066B maleate and m-trifluoromethylphenyl-piperazine hydrochloride; 5-HT2+IC, alpha methyl 5HT and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl; or 5-HT3, 2-methyl-5-hydroxytryptamine maleate and phenylbiguanide, agonists. Similarly, only the 5-HT1A antagonists, spiroxatrine and spiperone, attenuated the hyperalgesia induced by intradermally injected serotonin. 5-HT2+IC antagonists, mesulergine and ketanserin, and 5-HT3 antagonists, quipazine and 3-tropanyl-indole-3-carboxylate, did not significantly attenuate 5-HT hyperalgesia. We conclude that serotonin produces hyperalgesia by a direct action on the primary afferent neuron via the 5-HT1A subset of serotonin receptors.
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PMID:Serotonin is a directly-acting hyperalgesic agent in the rat. 153 74

Our work has focused on identifying the type of serotonin receptor through which serotonin acts as a developmental signal in the central nervous system. Previously, we have found that the regulation of development of ascending serotonergic neurons is through the balance of two serotonin receptors. One, the 5-HT1a receptor, releases a growth factor from astroglial cells. The other receptor is related to a release-regulating autoreceptor and can be stimulated indirectly by serotonin releasers such as fenfluramine. In the present study, we examined the receptors which regulate development of the descending neurons by treating pregnant rats with selective serotonergic drugs, from gestation day 12 until birth. Pups were subsequently tested for alterations in development by nociceptive testing (tail-flick latency) and by determining the binding of 3H-paroxetine, an indicator of serotonin terminal density, in spinal cord. Our results show that agents stimulating the 5-HT1a receptor (8-OH-DPAT) or the 5-HT1b receptor (TFMPP) or substances which release serotonin (fenfluramine) had no effect on the development of spinal serotonergic pathways. However, agents acting on the 5-HT3 receptor did--the agonist phenylbiguanide (PG) increased latency on tail-flick testing (postnatal days 10 and 30), while the antagonist, MDL 72222, decreased latency (postnatal days 10 and 18). Interestingly, both the agonist and the antagonist significantly increased 3H-paroxetine binding on postnatal day 18. Our results are discussed in terms of a possible mechanism by which 5-HT3 receptors may influence development.
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PMID:5-HT3 receptor-active drugs alter development of spinal serotonergic innervation: lack of effect of other serotonergic agents. 153 69

The hypothermia induced by the serotonin (5-HT)1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was attenuated in rats that had received a course of six electroconvulsive shocks (ECS) over a two-week period. The firing activity of dorsal raphe 5-HT neurons, as well as their responsiveness to microiontophoretic applications of 5-HT and 8-OH-DPAT, was unaltered in ECS-treated rats. The electrically evoked overflow of [3H]5-HT from preloaded slices of guinea pig hypothalamus was unchanged after the same ECS treatment. The concentration-effect curves of the 5-HT autoreceptor agonist 5-carboxyamidotryptamine (0.1-100 nM) were similar in slices prepared from control and ECS-treated guinea pigs. In addition, the reduction in the evoked [3H]5-HT overflow obtained by increasing the stimulation frequency from 1 to 5 Hz, which is due to a greater activation of terminal 5-HT autoreceptors at the higher frequency, was not altered by the ECS treatment. The enhancing effects of the 5-HT autoreceptor antagonist methiothepin (0.1-1 microM) and of the 5-HT3 agonist 2-methyl-5-HT (0.1-1 microM) on the evoked [3H]5-HT overflow were unaltered by the ECS treatment. These results thus indicate that repeated ECS attenuates the 8-OH-DPAT-induced hypothermia in rats, as previously reported, but does not affect the firing activity of 5-HT neurons and the sensitivity of their somatodendritic 5-HT1A autoreceptors in the dorsal raphe. The function of 5-HT terminals in the guinea pig hypothalamus was also unaffected by repeated ECS. In conclusion, repeated ECS does not affect the function of 5-HT neurons at the cell body and nerve terminal.
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PMID:Effect of repeated electroconvulsive shocks on serotonergic neurons. 153 97

We used saturation radioligand binding to measure nine types of serotonin receptors in 13 neuroblastomas from children. 5-HT1E and 5-HT3 sites were found in neuroblastomas with receptor density and affinity similar to human or rat brain. No 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2, or 5-HT uptake sites were found in any of the tumors, although all were detected in human or rat brain. These data demonstrate that human neuroblastomas possess 5-HT receptors found in human brain and relevant to human myoclonus. We speculate that 5-HT receptors in human neural crest-derived tumors may have clinical and neurobiological significance.
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PMID:Serotonin receptors in human neuroblastoma: a possible biologic tumor marker. 153 97

Eleven subtypes of central 5-HT receptor have so far been postulated, four of which have been cloned (5-HT1A, 5-HT1C, 5-HT1D and 5-HT2) and a fifth (the 5-HT3 receptor) purified. The present review discusses the agonists and antagonists which act at these subtypes with respect to their degree of selectivity and in vivo potency. Selective agonists exist for the 5-HT1A, 5-HT1B and 5-HT3 receptors and selective antagonists for the 5-HT2 and 5-HT3 receptors.
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PMID:Centrally active 5-HT receptor agonists and antagonists. 155 8

The acute and chronic effects of cocaine were evaluated on the 5-hydroxytryptamine (5-HT)-receptor 5-HT2 mediated behavioral function, the head-twitch response (HTR), in mice. In a recent study, we reported that the (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI)-induced HTR was dose dependently reduced by cocaine via indirect stimulation of serotonergic 5-HT1A and adrenergic alpha 2 receptors. In the present investigation, the HTR was evoked by the nonselective 5-HT agonist 5-methoxy-N,N-dimethyltryptamine hydrogen oxolate (5-MeO-DMT). Cocaine by itself failed to produce HTR but dose dependently inhibited the 5-MeO-DMT-induced behavior. Cocaine's effects were not due to 5-HT3 antagonism since acute administration of the more potent 5-HT3 antagonist (ICS-205,930) failed to produce or modify the 5-MeO-DMT-induced behavior. During withdrawal from chronic cocaine treatment (5-20 mg/kg), 5-MeO-DMT-induced HTR was enhanced. Depending upon the cocaine dose used, the induced supersensitivity persisted up to 172 h following cessation of cocaine treatment. The mechanisms of cocaine-induced supersensitivity were further investigated using the more selective 5-HT2 agonist DOI. Withdrawal from a low-dose (0.03-1.25 mg/kg) chronic cocaine treatment caused the DOI-induced HTR to increase, whereas withdrawal from a 5- and 10-mg/kg cocaine regimen had no significant effect. The maximal effect persisted up to 36 h following termination of cocaine treatment. Relative to vehicle-exposed controls, withdrawal from cocaine treatment enhanced the inhibitory potency of the 5-HT1A agonist (+-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT) on DOI-induced HTR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Repeated administration of low doses of cocaine enhances the sensitivity of 5-HT2 receptor function. 158 31

To study possible interactions between dopamine (DA) and serotonin (5-HT) neurochemical systems in the D-1 supersensitized induction of oral activity in neonatal 6-hydroxydopamine (6-OHDA) lesioned rats, the effects of a series of 5-HT agonists and antagonists were determined. At 3 days after birth rats were treated with desipramine HCl (20 mg/kg i.p., base form, 1 hr) and 6-OHDA HBr (100 micrograms, salt form, in each lateral ventricle). Rats were observed individually as adults, once a minute every 10 min over a 1-hr period after challenge with a DA or 5-HT receptor agonist. The respective 5-HT1A and 5-HT1B agonists, (+/-)-8-hydroxydipropylaminotetralin (0.50 mg/kg s.c.) and CGS 12066B maleate (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1, 2-alquinoxaline], 1:2 maleate salt; 3.0 mg/kg i.p.), did not increase oral activity. The mixed 5-HT1C and 5-HT2 receptor agonist, m-chlorophenylpiperazine (m-CPP), produced a slight increase in oral activity in control rats and a marked increase in oral activity in 6-OHDA-lesioned rats. In the 6-OHDA group the peak effect of 76.5 +/- 4.1 oral movements occurred with an m-CPP 2-HCl dose of 4.0 mg/kg. Pindolol (1.0 mg/kg i.p.), ketanserin tartrate (5 mg/kg i.p.) and MDL-72222 (3-tropanyl-3,5-dichlorobenzoate; 10 mg/kg s.c.), antagonists with high affinity for 5-HT1A,1B, 5-HT2 and 5-HT3 receptors, respectively, did not attenuate m-CPP actions. However, mianserin HCl (1.0 mg/kg s.c.), an antagonist with high affinity for 5-HT1C and 5-HT2 receptors, attenuated the oral response to m-CPP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Supersensitization of the oral response to SKF 38393 in neonatal 6-OHDA-lesioned rats is mediated through a serotonin system. 160 67


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