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 administration of the 5-HT1A agonist 8-OH-DPAT (0.8 mumols kg-1 s.c.-40 min) produced an increase in dopamine (DA) turnover, estimated by the quotient (DOPAC + HVA) DA-1, in the ventral striatum of the rat. No statistically significant effects were obtained in the dorsal striatum. The accumulation of 3-MT in pargyline-treated animals (375 mumols kg-1 s.c.-60 min) was not affected by 8-OH-DPAT treatment (0.15-2.4 mumols kg-1 s.c.-30 min). These findings indicate that 8-OH-DPAT has weak antagonist properties at striatal DA receptors in normal rats. Both the 5-HT1A agonist flesinoxan (0.06-17.8 mumos kg-1 s.c. -50 min) and the mixed 5-HT1 and 5-HT2 agonist 5-MeODMT (1.6-26.0 mumols kg-1 s.c.-50 min) produced a decrease in forebrain 5-HTP accumulation (striatum and neocortex), following decarboxylase inhibition by means of NSD-1015 in reserpine treated rats, indicating stimulation of central 5-HT receptors by these two compounds. At the same time, the DOPA accumulation by the ventral striatum was decreased by flesinoxan and increased by 5-MeODMT treatment. These observations show that, under these conditions, the decrease in DA synthesis is not directly coupled to the decreased 5-HT synthesis produced by flesinoxan, as previously demonstrated for 8-OH-DPAT. Taken together with previous observations, the present results suggest that 8-OH-DPAT, depending on the experimental conditions, is an agonist or antagonist at striatal DA receptors, in all probability due to partial DA receptor agonist properties of the compound.
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PMID:Increased dopamine turnover in the ventral striatum by 8-OH-DPAT administration in the rat. 197

1. The possibility of 5-HT2 receptor modulation of central 5-HT1A receptor function has been examined using the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-HT1A receptor active drugs in rats. 2. The 5-HT2/5-HTIC antagonist ritanserin (0.1-2 mg kg-1) increased the 5-HT behavioural syndrome induced by submaximally effective doses of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and gepirone. 3. Pretreatment with the 5-HT2/5-HT1C antagonist ICI 170,809 (0.25-5 mg kg-1) also enhanced the behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT. 4. The 5-HT2/alpha 1-adrenoceptor antagonist ketanserin in a low dose (0.25 mg kg-1) significantly increased the 5-HT behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT, while in a higher dose (2.5 mg kg-1) this drug decreased the response. Experiments with prazosin indicate that the higher dose of ketanserin might reduce the 5-HT behavioural syndrome through blockade of alpha 1-adrenoceptors. 5. Ritanserin and ICI 170,809 had no effect on apomorphine-induced stereotypy or hyperactivity, indicating that these drugs do not produce non-specific behavioural activation. 6. Ritanserin and ICI 170,809 inhibited quipazine-induced wet dog shakes at doses similar to those enhancing the 5-HT behavioural syndrome. 7. We suggest that ritanserin, ICI 170,809 and ketanserin enhance 5-HT1A agonist-induced behaviour through blockade of an inhibitory 5-HT2 receptor regulating or coupled to 5-HT1A receptor-mediated function.
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PMID:Behavioural evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors. 214 51

The role of the 5-hydroxytryptamine (5-HT) receptor subtypes in the spinal cord in the regulation of nociception is unknown. This study examined whether administration of different 5-HT1 receptor agonists into the spinal subarachnoid space of mice modulates the nociceptive tail-flick reflex, and whether effects on the tail-flick reflex involve changes in tail skin temperature. The tail-flick latencies (the time needed to evoke the tail-flick reflex by noxious radiant heat) were significantly increased after intrathecal (i. th.) injection of 5-HT (10-20 micrograms), the 5-HT1A/5-HT1B receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 10-20 micrograms), the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 20 micrograms) and after i.th. injection of 1(m-chlorophenyl)piperazine (mCPP, 5-20 micrograms) and 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969, 5-20 micrograms) which have high affinity for the 5-HT1B receptors. None of the 5-HT1 receptor agonists had the ability to change the tail skin temperature. The results show that in the mouse i.th. injection of both 5-HT1A and 5-HT1B receptor agonists has the ability to inhibit the tail-flick reflex without interfering with the tail skin temperature.
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PMID:The role of spinal cord 5-HT1A and 5-HT1B receptors in the modulation of a spinal nociceptive reflex. 215 Jul 69

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 effects of a variety of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on behaviour in 5- and 20-day old rat pups have been investigated. Increased locomotion and head-weaving responses were induced in both age groups by 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin; 5-HT1A agonist); 5-MeODMT (5-methoxy-N,N-dimethyltryptamine; 5-HT1) and RU 24969 (5-methoxy-3(1,2,3,6-tetrahydropyrindin-4-yl)-1H-indole; 5-HT1B/5-5HT1A). The putative 5-HT1A-agonist LY165163 (1-2-(4-aminophenyl)ethyl 4-(3-trifluoromethylphenyl)piperazine) also produced hyperactivity in the developing pups. In contrast, locomotion was not affected by buspirone (5-HT1A); mCPP (1-(3-chlorophenyl)piperazine; 5-HT1B/5-HT1C) and DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane; 5-HT2) though buspirone produced a small increase in head-weaving at 5- and 20-days. The full 5-HT syndrome was induced in older animals (but not neonates) by both 8-OH-DPAT and 5-MeODMT. Large doses of buspirone, mCPP and DOI also produced signs of reciprocal forepaw treading and flattened body posture at 20-days. In addition, mCPP induced grooming and stereotyped mouthing, while DOI increased sniffing behaviour in the young rats. Catecholaminergic mechanisms were implicated in the head-weaving and locomotor responses to 8-OH-DPAT and RU 24969, following experiments with a number of monoamine receptor antagonists. Preliminary findings with (-)-pindolol, which was high affinity for 5-HT1-receptors, suggested that this subtype of receptor may play a role in hyperlocomotion induced by RU 24969.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavioural profiles of putative 5-hydroxytryptamine receptor agonists and antagonists in developing rats. 252 30

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

The repeated administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 3 mg/kg, twice daily for 14 days) significantly diminished hypothermia and corticosterone secretion induced by an acute challenge with the 5-HT1A agonist 8-OH-DPAT (0.1 mg/kg) when compared to the responses in animals treated chronically with the solvent vehicle. In contrast, the chronic administration of 5-MeODMT did not alter the magnitude of hyperthermia or corticosterone secretion induced by the acute administration of MK-212 (1.0 mg/kg). The repeated administration of the 5-HT2 agonist DOI (1.0 mg/kg, daily for 7 days) significantly reduced the increase in corticosterone, but not body temperature, produced by MK-212. Chronic treatment with DOI did not alter the hypothermia or increase in corticosterone secretion elicited by 8-OH-DPAT. These data are consistent with other evidence that these physiological effects of 8-OH-DPAT and MK-212 are mediated by 5-HT1A and 5-HT2 receptors, respectively. Thus, data presented in these studies are suggestive that the chronic administration of 5-MeODMT diminishes the responsiveness of 5-HT1A receptor-mediated changes in body temperature and corticosterone secretion without altering the responses mediated by 5-HT2 receptors. In contrast, the chronic administration of DOI selectively diminishes the magnitude of 5-HT2 receptor-mediated changes in corticosterone secretion without affecting the responsiveness of those receptors involved in thermoregulatory responses. These selective changes in receptor responsiveness following the chronic administration of these 5-HT agonists further establishes the independence of 5-HT1A and 5-HT2 receptor-mediated pharmacological effects.
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PMID:Selective cross-tolerance to 5-HT1A and 5-HT2 receptor-mediated temperature and corticosterone responses. 253 56

1. The abilities of two indole agonists and some nonindole agonists to induce relaxation of catch contraction and the influence of the agonists on cyclic AMP (cAMP) levels in the anterior byssus retractor muscle (ABRM) of Mytilus were investigated. 2. 5-MeOT (5-methoxytryptamine) and 5-MeODMT (5-methoxy-N,N-dimethyltryptamine) dose-dependently relaxed the contraction. 3. TFMPP (m-trifluoromethylphenyl piperazine), PAPP (p-amino-phenyl TFMPP) and mCPP (1-(3-chlorophenyl)piperazine dose-dependently relaxed the contraction, but 2MPP (1-(2-methylphenyl) piperazine and quipazine did not. 4. 5-MeOT (10(-6)M), 5-MeODMT (10(-6)M), TFMPP (10(-4)M), 2MPP (10(-4)M), quipazine (10(-4)M) and 8-OH-DPAT (3 x 10(-5) M) significantly reduced the cAMP levels, but PAPP (3 x 10(-4)M) and mCPP (10(-4)M) did not have any effect on cAMP levels. 5. These findings indicate that the pharmacological properties of 5-HT1-like receptors in the ABRM are similar to those of 5-HT1A receptors in mammalian tissues, and that the changes in cAMP levels induced by the agonists used are unlikely to be directly linked to the relaxation induced by them.
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PMID:The relaxation induced by indole and nonindole 5-HT agonists in the molluscan smooth muscle. 290 67

The 5-HT receptor subtypes involved in the mediation of reciprocal forepaw treading and the flat body posture induced by the central 5-HT receptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), were examined in intact rats and in rats depleted of monoamines with reserpine. Forepaw treading in non-reserpinised rats was antagonised by the 5-HT2 receptor antagonist, ketanserin, only at doses in excess of those required for occupation of a large proportion of 5-HT2 receptors in brain, and at which there was significant inhibition of stereotyped sniffing induced by the dopamine receptor agonist, apomorphine. Since forepaw treading induced by 5-MeODMT was also blocked in intact rats by haloperidol, blockade of the behaviour by ketanserin may more accurately reflect antagonism at dopamine receptors than at 5-HT2 receptors. In reserpinised rats, i.e. with minimised contributions from other monoamine systems, neither forepaw treading nor the flat body posture were significantly altered by ketanserin, haloperidol or the beta 1- and beta 2-selective adrenoceptor antagonists, betaxolol and ICI 118.551, making a key role for 5-HT2 receptors, dopamine receptors and beta-adrenoceptors unlikely. In contrast, forepaw treading in both reserpinised and non-reserpinised rats was antagonised stereoselectively by pindolol and by spiperone, which interact with 5-HT1 and 5-HT1A recognition sites. The results are consistent with the hypothesis that forepaw treading induced by 5-MeODMT arises by activation of the putative 5-HT1A receptor. Antagonism of the flat body posture by pindolol could be demonstrated only in non-reserpinised rats and the mechanism of induction of this behaviour remains to be established.
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PMID:Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat. 293 8

The effects of serotonergic agonists and antagonists on the body temperatures of rats were investigated. The administration of the serotonin (5-HT) agonist 6-chloro-2(1-piperazinyl)-pyrazine (MK-212) produced a dose-related increase in body temperature. A maximal increase in body temperature of approx. 1.1 degrees C was observed 30 min after the administration of 3 mg/kg of MK-212. In contrast, administration of the putative 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) resulted in marked, dose-related hypothermic responses. Body temperatures were decreased approx. 3 degrees C 30 min after an injection of 0.3 mg/kg of 8-OH-DPAT. Body temperatures were affected differentially by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). Large doses (3-10 mg/kg) of 5-MeODMT elicited hyperthermic responses, whereas small doses (0.5-1.0 mg/kg) produced hypothermic responses. Treatment of rats with ketanserin (3 mg/kg) completely prevented the hyperthermic effects of 5-MeODMT, and, in fact, converted a hyperthermic response to 5-MeODMT into a marked hypothermic response. Ketanserin (0.1-1.0 mg/kg) selectively antagonized the hyperthermic response to MK-212 but did not alter the hypothermic effect of 8-OH-DPAT. Mianserin (10 mg/kg) and pirenperone (0.03 mg/kg) also selectively antagonized hyperthermia induced by MK-212. In contrast, pindolol (0.03-0.1 mg/kg) and methiothepin (10 mg/kg) selectively antagonized hypothermia induced by 8-OH-DPAT but did not alter hyperthermia induced by MK-212. Spiperone (0.1-3 mg/kg) and pizotifen (10 mg/kg) attenuated the effects of both 8-OH-DPAT and MK-212. Xylamidine, a peripheral 5-HT antagonist, had no significant effect on hyperthermia induced by MK-212 or hypothermia induced by 8-OH-DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat. Evidence for opposing roles of 5-HT2 and 5-HT1A receptors. 295 11


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