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)

Research has indicated that serotonin (5-HT) is involved in regulating male sexual behavior in rodent, as well as primate species. The present study was designed to further characterize 5-HT influences on male sexual behavior of rhesus monkeys. Experiment 1 examined the effects of 5-HT1A and 5-HT1C/1D receptor stimulation on penile erections and yawning behavior. Administration of the 5-HT1C/1D receptor agonist, m-chlorophenylpiperazine (m-CPP, 0.8 and 3.0 mg/kg), facilitated the occurrence of penile erection, and at doses greater than 0.2 mg/kg stimulated yawning. By contrast, the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.01-0.2 mg/kg) did not significantly influence penile erections or yawning behavior. Experiment 2 evaluated the effects of m-CPP and 8-OH-DPAT on the behavior of male monkeys in the presence of a sexually receptive female monkey which the males could see, hear and smell, but not physically contact. Administration of m-CPP along with presentation of a receptive female stimulated penile erections to a greater extent than they were stimulated by either one of these manipulations alone. Administration of 8-OH-DPAT (0.1 and 0.2 mg/kg) produced a decrease in the percent of monkeys exhibiting penile erections in the presence of the female. In this experiment, yawning was affected in opposite directions, with m-CPP stimulating and 8-OH-DPAT decreasing the frequency of yawning. Experiment 3 assessed the effects of m-CPP on male copulatory behavior of rhesus monkeys. Administration of m-CPP (0.8-3.0 mg/kg) produced a dose-dependent decline in the percent of males initiating copulation and achieving ejaculation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5-HT1A and 5-HT1C/1D receptor agonists produce reciprocal effects on male sexual behavior of rhesus monkeys. 827 74

To study interactions between DA and 5-HT neurochemical systems in the DA D1 supersensitized induction of oral activity in neonatal 6-hydroxydopamine (6-OHDA) lesioned rats, the effects of a variety of 5-HT receptor agonists and antagonists were determined. At 3 days after birth rats were treated with desipramine HCl (20 mg/kg i.p., base form) 1 h before 6-OHDA HBr (100 micrograms, salt form, in each lateral ventricle). When these rats were studied as adults it was determined that the striatal content of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was reduced by 98%, while the striatal content of 5-HT was elevated by 75%. The Bmax and Kd for [3H]SCH 23390 and [3H]spiperone binding to striatal homogenates was unaltered in the lesioned rats. However, oral activity responses to a D1 agonist (SKF 38393), D2 antagonist (spiperone) and 5-HT1C agonist [1-(3-chlorophenyl)piperazine] were enhanced several fold in the lesioned rats. Several other agonists and antagonists that act at 5-HT1A, 5-HT1B, 5-HT2 and 5-HT3 receptors did not produce an altered response in the lesioned rats, nor were these substances effective in attenuating m-CPP-enhanced oral activity responses. The DA D1 receptor antagonist, SCH 23390 HCl (0.30 mg/kg i.p.), did not attenuate the response to m-CPP 2HCl (1.0 mg/kg i.p.). However, the 5-HT receptor antagonist, mianserin HCl (1.0 mg/kg s.c.) did effectively attenuate the oral activity response to SKF 38393 HCl (1.0 mg/kg i.p.). These findings indicate that there is supersensitization of both DA D1 and 5-HT1C receptors in neonatal 6-OHDA-lesioned rats, and that a D1 agonist acts via the 5-HT1C receptors. Therefore, induction of oral activity by DA agonists occurs through a serotoninergic neurochemical system.
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PMID:Serotonin (5-HT) systems mediate dopamine (DA) receptor supersensitivity. 831 65

The effect of chronic treatment (5 and 10 mg/kg i.p., twice daily, 14 days) with fluoxetine (FLU), an antidepressant drug which selectively inhibits the reuptake of 5-hydroxytryptamine (5-HT), on the responsiveness of 5-HT receptor subpopulations to their agonists in rats and mice was examined. FLU had no effect on the hypothermia (in mice) and the behavioural syndrome (in rats) induced by 8-OH-DPAT (a 5-HT1A agonist). The m-CPP-induced hypothermia in mice (a 5-HT1B effect) was increased by FLU given chronically. FLU in a single dose decreased that effect. FLU given chronically attenuated the m-CPP-induced hypoactivity in rats (a 5-HT1C effect). The effects mediated by 5-HT2 receptors (L-5-HTP-induced head twitches in mice; fenfluramine-, m-CPP- and TFMPP-induced hyperthermias in rats) were reduced by chronic FLU. The above results indicate that FLU given chronically has no effect on the responsiveness of 5-HT1A receptors, increases the responsiveness of 5-HT1B receptors and decreases those of 5-HT1C and 5-HT2 receptors.
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PMID:Effects of fluoxetine given chronically on the responsiveness of 5-HT receptor subpopulations to their agonists. 836 53

The present study was undertaken to evaluate the serotonin (5-HT) receptor subtype(s) by which 5-HT acts on the pituitary to stimulate ACTH secretion. We tested the effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), the 5-HT1C receptor agonist metachloro-phenylpiperazine (m-CPP), which also binds to other 5-HT receptors with lower affinity, and the 5-HT2/1C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on basal, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP)-stimulated ACTH release from primary rat anterior pituitary cell cultures. 5-HT, 8-OH-DPAT and DOI significantly increased basal ACTH release, an effect which was antagonized by 5-HT receptor antagonists. 5-HT and DOI were effective at nanomolar concentrations whereas 8-OH-DPAT was effective at higher concentrations. 5-HT, 8-OH-DPAT (both at 10 nmol/l) and DOI (at higher concentrations) blunted the stimulatory effect of CRH. The suppressive effects of 8-OH-DPAT and DOI on CRH-stimulated ACTH release were antagonized by (-)propranolol, a beta-adrenergic receptor antagonist which binds the 5-HT1A receptor with elevated affinity, and ketanserin, a 5-HT2 receptor antagonist respectively. 5-HT, 8-OH-DPAT and DOI showed additive stimulatory effects with AVP but only at the highest concentration tested, whereas m-CPP potentiated AVP-induced ACTH release at concentrations of 1 nmol/l or more. This effect was antagonized by metergoline, a non-selective 5-HT receptor antagonist and mianserin, an antagonist which binds the 5-HT1C receptor with elevated affinity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of selective serotonin agonists on basal, corticotrophin-releasing hormone- and vasopressin-induced ACTH release in vitro from rat pituitary cells. 838 13

The effect of repeated administration of (+)-OXA (a noradrenaline (NA) uptake inhibitor) and (-)-OXA (devoid of an effect on the NA uptake, but a clinically active antidepressant drug) on central 5-HT receptor subpopulations was studied. (-)-OXA given repeatedly, but not acutely, attenuated the 8-OH-DPAT-induced hypothermia in mice. (+)-OXA administered acutely, as well as repeatedly, was inactive in that test. The 8-OH-DPAT-induced syndrome in rats was attenuated by both OXA isomers administered either acutely or repeatedly. The hypothermia induced by m-CPP in mice was attenuated by single-dose administration of (+)-OXA and (-)-OXA; when given repeatedly, (+)-OXA increased the action of m-CPP. (-)-OXA administered repeatedly was inactive in that test. Either single or repeated administration of (+)-OXA had practically no effect on the depression of exploratory activity induced by m-CPP. (-)-OXA administered acutely or repeatedly attenuated the effect of m-CPP in the same manner. Acute, but not chronic, administration of (-)-OXA reduced the number of head-twitch episodes induced by 5-HTP in mice. Repeated, but not acute, treatment with (+)-OXA attenuated the effect of 5-HTP. The obtained results indicate that (+)-OXA administered repeatedly increases the reactivity of 5-HT1B receptors, decreases the reactivity of 5-HT2 receptors, and has no effect on the reactivity of 5-HT1A- (pre- and postsynaptic) and 5-HT1C-receptors. (-)-OXA given repeatedly decreases the reactivity of presynaptic 5-HT1A receptors and has no influence on the reactivity of postsynaptic 5-HT1A-, 5-HT1B-, 5-HT1C- and 5-HT2-receptors.
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PMID:The effect of repeated treatment with oxaprotiline enantiomers on central 5-HT receptor subpopulations. 840 66

The effect of various psychotropic drugs on the ambivalent behaviour "stretched approach posture" (SAP) in the rat was assessed. SAP was elicited after a mild startle reaction due to physical contact with an electrified prod at one end of a straight runway. Using ethological observation methods, SAP as well as intention movements, prod contact, crossings, rearing, exploration, grooming and immobility were recorded. The benzodiazepine receptor agonists chlordiazepoxide, diazepam and alprazolam, the 5-HT1A receptor agonists flesinoxan and ipsapirone and the 5-HT uptake inhibitor clomipramine selectively (no effect on crossings) reduced SAP. Except for alprazolam, these drugs also reduced intention movements. In addition, chlordiazepoxide and diazepam enhanced prod contact. Reductions of SAP and intentions with concomitant reductions of crossings (nonspecific antiambivalent effects) were established for the alpha 2-adrenoceptor agonist clonidine and the MAO inhibitor clorgyline. The 5-HT uptake inhibitor fluvoxamine suppressed intention movements, but not SAP. The mixed 5-HT/NA uptake inhibitor imipramine did not significantly affect SAP or intentions, but reduced crossings. The 5-HT2C/1B receptor agonist m-CPP, the inverse BZD receptor agonists FG 7142 and DMCM, and the alpha 2-adrenoceptor antagonist yohimbine, to all of which putative anxiogenic effects have been ascribed, had no effect on SAP directed towards the prod. m-CPP, however, produced an increase in the stretched posture directed away from the prod (SAwayP). FG 7142 reduced intentions while strongly enhancing immobility (freezing). SAwayP and/or freezing may possibly reflect anxiogenic properties of drugs. The putative anxiogenic drug pentylenetetrazol false positively reduced SAP while increasing exploration. The dopamine-D2 receptor antagonist haloperidol and the catecholamine releaser dl-amphetamine had no effect on ambivalent behaviour. The muscarine receptor antagonist scopolamine reduced SAP and intentions while stimulating crossings. Finally, the 5-HT2C receptor antagonist ritanserine, the CCKA receptor antagonist devazepide, the CCKB receptor antagonist L-365.260 and the strychnine-insensitive glycine site antagonist 7-Cl-kynurenic acid were without effect on the behaviours in this paradigm using single doses. In conclusion, SAP and intention movements were reduced selectively by anxiolytic agents from different classes, including benzodiazepine receptor agonists, 5-HT1A receptor agonists and a 5-HT uptake inhibitor, whereas an alpha 2-adrenoceptor agonist and a MAO inhibitor reduced SAP non-selectively. SAP in relation to other behaviours may therefore serve as a valuable paradigm to characterize anxiolytic drugs.
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PMID:The ambivalent behaviour "stretched approach posture" in the rat as a paradigm to characterize anxiolytic drugs. 853 44

In mice injected with formalin into the hindpaw, the 5-HT1A receptor agonists, 8-OH-DPAT and flesinoxan, equipotently inhibited the early phase (EP) and late phase (LP) of licking. At higher doses, they provoked ataxia and inhibited the writhing elicited by intra-abdominal acetic acid. The antagonists, (-)-alprenolol, (-)-tertatolol, WAY-100,135 and S 15931 were more potent against the LP than the EP. They also inhibited writhing, and only at very high doses did they elicit ataxia. In rats, 8-OH-DPAT and flesinoxan increased the current required to elicit vocalisation upon electrical stimulation of the tail. The action of 8-OH-DPAT was blocked by WAY-100,135, which, like other antagonists, was inactive alone. Interestingly, a low dose of 8-OH-DPAT partially inhibited the antinociceptive action of the mu-opioid agonist, morphine, the action of which was dose-dependently facilitated by (-)-alprenolol and S 15931. Administered s.c., 8-OH-DPAT elicited spontaneous tail-flicks (STFs) in rats: these were abolished by WAY-100,135, (-)-tertatolol, (-)-alprenolol and S 15931. STFs were also eliminated by s.c. or i.t. administration of the alpha 2-adrenergic receptor agonist, clonidine, the GABAA agonist, muscimol or the GABAB agonist, baclofen. The mu-opioid, morphine, blocked STFs only at high doses and the kappa-opioid agonists, U 50,488 and U 69,593, even at supra-ataxic doses, were inactive. Antagonists at neurokinin (NK)1 (RP 67580), NK2 (SR 48,968) and bradykinin (BK)2 (Hoe 140) receptors, as well as aspirin, did not block STFs, though indomethacin was effective. Antagonists at the glycine B site coupled to the NMDA receptor, L 687,414, L 701,324 and (+)-HA966, blocked STFs. Furthermore, (+)-HA 966 and the competitive NMDA receptor antagonist, CPP, were active upon i.t. administration. STFs were also blocked by s.c. or i.t. administration of the AMPA antagonists, YM 900 and NBQX. In conclusion, the influence of 5-HT1A ligands upon nociception is dependent upon the algesiometric paradigm. Intriguingly, modulation of 5-HT1A receptor-mediated STFs reveals parallels to neuropathic pain.
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PMID:Pro- and antinociceptive actions of serotonin (5-HT)1A agonists and antagonists in rodents: relationship to algesiometric paradigm. 878 80

To test the hypothesis that the mechanisms of 5-HT1 and 5-HT2 receptor-mediated hormonal responses are different, we compared the effects of hypothalamic paraventricular nucleus (PVN) lesions on the ACTH/corticosterone, prolactin and oxytocin responses to the 5-HT1A agonist ipsapirone (1 and 2 mg/kg), the 5-HT2C agonist m-chlorophenylpiperazine (m-CPP, 0.6 mg/kg), which also binds to other 5-HT receptors with lower affinity, and the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg) in chronically cannulated, freely moving male rats. Pharmacological characterization using antagonists with different affinity for 5-HT2A and 5-HT2C receptors revealed that DOI's responses were mediated mainly by 5-HT2A receptors and m-CPP's responses were almost exclusively mediated by 5-HT2C receptors. ACTH/corticosterone responses to ipsapirone, DOI and m-CPP were almost completely blocked after PVN lesions. Prolactin responses were significantly different in lesioned rats only after DOI and m-CPP challenges. Oxytocin responses to ipsapirone and DOI, but not m-CPP were markedly attenuated after PVN lesions. The present findings suggest that the PVN, or neural pathways close to it, mediate corticosterone and in some cases prolactin and oxytocin responses to selective stimulation of 5-HT1A, 5-HT2A, or 5-HT2C receptors.
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PMID:Role of the hypothalamic paraventricular nucleus in 5-HT1A, 5-HT2A and 5-HT2C receptor-mediated oxytocin, prolactin and ACTH/corticosterone responses. 878 18

The effects of the Ca2+ and 5-HT1 and 5-HT2 receptor antagonist dotarizine and of some other agonists and antagonists of different 5-HT receptor subtypes administered alone or in combination with the 5-HT uptake inhibitor fluoxetine (FLU) on nociception were studied, using a foot-pressure method (analgesy-meter testing). Dotarizine (DOT) administered at a dose of 50 mg/kg for 3 days orally significantly increased the pain threshold. Fluoxetine (FLU) administered at a dose of 10 mg/kg for 3 days also significantly increased the pain threshold. The combination of DOT and FLU abolished the analgesic effects of the two drugs. The 5-HT1A and 5-HT1B/1C receptor agonists buspirone and m-CPP decreased the pain threshold. The antagonists of 5-HT1A(NAN-190),5-HT1/5-HT2(methysergide), 5-HT2 (ritanserin), and 5-HT3 (ondansetron) receptors as well as the agonists of 5-HT2(DOI) and 5-HT3 (mCPBG) receptors increased the pain threshold. Fluoxetine at a single dose of 10 mg/kg differently influenced the effects of the 5-HT agonists and antagonists on nociception. Comparison of the effects of dotarizine with the effects of some of the agonists and antagonists of 5-HT receptor subtypes on the nociceptive and other actions suggests the possibility of a therapeutic value of dotarizine as an antimigraine drug.
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PMID:Effects on nociception of the Ca2+ and 5-HT antagonist dotarizine and other 5-HT receptor agonists and antagonists. 883 Aug 81

Intraperitoneal administration of m-chlorophenylpiperazine (m-CPP) to Wistar rats produced hyperthermia with a peak effect at 30 min. Pretreatment with low doses of metergoline (5-HT1/5-HT2 antagonist), mesulergine and mianserin (5-HT2C/5-HT2A antagonists) blocked m-CPP-induced hyperthermia. Pretreatment with propranolol (beta-adrenergic receptor antagonist that also has binding affinity for 5-HT1A, 5-HT1B and 5-HT2B sites), yohimbine (alpha 2-noradrenergic antagonist that also has binding affinity for 5-HT2B sites), MDL-72222 or ondansetron (5-HT3 antagonists) did not attenuate m-CPP-induced hyperthermia. Only high doses of ketanserin, LY-53857 and ritanserin (5-HT2A/5-HT2C antagonists) as well as spiperone (5-HT1A/5-HT2A/D2 antagonist) attenuated m-CPP-induced hyperthermia. Daily administration of m-CPP produced complete tolerance to its hyperthermic effect by day 5. However, there was no cross-tolerance to 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, a 5-HT2A agonist that also has high affinity for 5-HT2C receptors)-induced hyperthermia. m-CPP-induced increases in temperature were found to be significantly less in the Fawn-Hooded (FH) rat strain as compared to the Wistar rat strain; in prior studies, FH rats have been found to be subsensitive to other 5-HT2C-mediated pharmacologic responses. Altogether, these findings suggest that m-CPP-induced hyperthermia in rats is mediated by selective stimulation of 5-HT2C receptors.
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PMID:Evidence that m-chlorophenylpiperazine-induced hyperthermia in rats is mediated by stimulation of 5-HT2C receptors. 886 72


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