Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of conditioned fear stress (CFS) on 5-HT release in the medial prefrontal cortex were studied by in vivo microdialysis. CFS (exposure to an environment in which foot-shock had been delivered previously) induced a marked suppression of motility-that is, freezing behavior. The extracellular concentration of 5-HT in the medial prefrontal cortex increased during this freezing behavior, but no significant changes were observed in the concentration of its metabolite, 5-HIAA. The increased 5-HT concentration returned to pretreatment levels when the animals were returned to their home cages. Diazepam (0.5 mg/kg, intraperitoneally) reduced the CFS-induced freezing behavior and prevented the increases in extracellular 5-HT levels. A 5-HT3 receptor antagonist, tropisetron (10 and 100 micrograms/kg), also inhibited both the CFS-induced increase in 5-HT release and the freezing behavior. These findings suggest that there is a relationship between anxiety and 5-HT release in the prefrontal cortex and that the 5-HT3 receptor antagonist tropisetron might have anxiolytic properties.
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PMID:Effects of conditioned fear stress on 5-HT release in the rat prefrontal cortex. 766 78

1. We devised a new light/dark transition apparatus, recorded transitions, % time animals spent outside the dark chambers (% time) and locomotor activity, and evaluated this apparatus by testing anxiolytics, non-anxiolytic drugs and putative anxiogenic drugs in mice. 2. Diazepam and alprazolam significantly increased transitions, % time and locomotor activity. The effects of 1 mg/kg (i.p.) diazepam on these parameters in this modified test were blocked by flumazenil, a selective benzodiazepine antagonist. 3. Anxiogenic drugs such as beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) and picrotoxin significantly decreased all three parameters. Another anxiogenic drug, yohimbine, also significantly decreased transitions and locomotor activity, but it significantly increased % time at 5 mg/kg (i.p.). 4. Imipramine (5-10 mg/kg, i.p.), an antidepressant, sulpiride (10-25 mg/kg, i.p.), an antipsychotic drug, and scopolamine (0.1-1 mg/kg, i.p.), an anticholinergic drug, had no effect. 5. Buspirone, a partial 5-HT1A receptor agonist, produced parameter changes similar to those induced by anxiolytic benzodiazepines. 8-OH-DPAT, a full 5-HT1A receptor agonist, significantly increased transitions and locomotor activity but not % time. 5-HT3 receptor antagonists, ICS205-930 and MDL72222, did not have any effect on these parameters. 6. Methamphetamine (1-2 mg/kg, i.p.) increased all parameters, while caffeine increased only locomotor activity. 7. The present findings indicate that the modified light/dark transition test is very simple and easy to perform for testing the anxiolytic and anxiogenic effects of drugs.
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PMID:The modified light/dark transition test in mice: evaluation of classic and putative anxiolytic and anxiogenic drugs. 771 61

VA21B7 (3-[2-(4'-piperonylpiperazinyl) indolyl] carboxaldehyde) was synthesized as a potential 5-HT3 receptor antagonist. Even though VA21B7 showed a higher affinity towards 5-HT3 receptors as compared to other receptors studied, it was not a potent 5-HT3 receptor antagonist either in the periphery or in the brain. In a simple animal model of anxiety such as the two-compartment box in mice, a remarkable anxiolytic-like effect was found at doses of 2-500 micrograms/kg IP and also at low oral doses, in the microgram range. These drug doses did not produce any significant effect on spontaneous motor activity of mice. The anxiolytic profile of VA21B7 was further explored using other models of anxiety in rats such as the elevated plus-maze and punished-drinking. VA21B7 was compared with standard 5-HT3 receptor antagonists such as ondansetron, tropisetron and granisetron, with the 5-HT1A agent buspirone and with diazepam. In the plus-maze, VA21B7 showed an anxiolytic-like profile after doses of 0.25-0.5 mg/kg IP or 2-4 mg/kg PO which did not modify the number of total entries into the open and closed arms of the maze. Diazepam, granisetron and tropisetron were also effective in this test but not ondansetron and buspirone. VA21B7 was also able to release suppressed behaviour in the punished-drinking test. The dose-response curve was bell-shaped with a peak at 2-4 mg/kg. At variance with other studies, 5-HT3 receptor antagonists also increased the number of shocks taken in this test and the dose-response curve was also bell-shaped. VA21B7 was not anticonvulsant like diazepam, its anxiolytic action in the light/dark test was not flumazenil-sensitive and there was no rebound anxiogenic effect on withdrawal from chronic VA21B7 treatment for 15 consecutive days. Moreover, VA21B7 was not amnesic like the benzodiazepines but low doses of 2-4 mg/kg reduced the memory deficits induced in rats by scopolamine. Much higher doses were necessary to decrease spontaneous motor activity in rats. Since VA21B7 appears to be well tolerated in rodents at high doses, we think that it is of potential interest as an anxiolytic in humans.
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PMID:The pharmacology of VA21B7: an atypical 5-HT3 receptor antagonist with anxiolytic-like properties in animal models. 775 59

The cholecystokininB receptor antagonist CI-988 ([R-(R*,R*)]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2- [[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]amino]- propyl]amino]-1-phenylethyl]amino]-4-oxobutanoic acid compound with 1-deoxy-1-(methylamino)-D-glucitol (1:1)) and the benzodiazepine receptor agonist diazepam were tested for potential anxiolytic effects on punished exploratory behavior in the four-plate test using mice. Diazepam (0.31-5 mg/kg PO) increased the number of shocks taken in a dose-dependent manner, an effect blocked by the benzodiazepine receptor antagonist flumazenil. CI-988 (0.00001-1 mg/kg PO) tended to increase the number of delivered shocks over the chosen dose range; this effect was, however, not dose-related or as large as that produced by diazepam. A limited testing of the 5-hydroxytryptamine3 receptor antagonist ondansetron (0.1 and 1 mg/kg PO) suggested an effect similar to CI-988. These results indicate that distinct and contrasting dose-response profiles exist for these classical and atypical drugs in an animal model of anxiety based on electric shock.
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PMID:Differential profile of the CCKB receptor antagonist CI-988 and diazepam in the four-plate test. 787 Oct 56

Anxiety disorders are the most common behavioral disorders, and they exhibit high comorbidity rates. The aim of the present study was to confirm the effects of Amibegron, the first selective beta 3 adrenergic agent, on anxiety and to demonstrate that different serotoninergic receptor subtypes are involved in this effect. We administered the serotonin 5-HT1A receptor antagonist WAY-100635, the serotonin 5-HT2A receptor antagonist Ketanserin and the serotonin 5-HT3 receptor antagonist Ondansetron in mice and evaluated their performance in the elevated plus-maze test. Mice administered with Amibegron (5 and 10 mg/kg) showed a dose-dependent prolonged time spent in the open arms and an increase in the number of entries into the open arms during the elevated plus-maze (EPM) test. However, in the control mice, administration of WAY, Ketanserin and Ondansetron demonstrated no effect on the time spent in the open arms and the number of entries into the open arms. In addition, these treatments all significantly reversed the effect of the Amibegron-induced (10 mg/kg) increase in the time spent in the open arms. However, only WAY and Ketanserin treatments reversed the Amibegron-induced increase in the number of entries into the open arms. In conclusion, Amibegron exerted a significant anxiolytic effect, which was as effective as Diazepam, in mice during the EPM test. This effect of Amibegron may be mediated by interactions with the serotonin 5-HT1A, 5-HT2A and 5-HT3 receptors.
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PMID:Evidence that the anxiolytic-like effects of the beta3 receptor agonist amibegron involve serotoninergic receptor activity. 2375 83