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 5-HT3 receptor antagonist BRL 43694 was administered in drinking fluid to Mongolian gerbils, previously selected for their propensity to exhibit seizures on mild stimulation, for 11 days at doses of 1.5 micrograms/kg, 150 micrograms/kg and 1 mg/kg daily, while controls received tap water. Effects upon behaviour during encounters under white light with an untreated resident gerbil were assessed using ethological procedures. Effects upon seizure susceptibility and severity were also examined. All doses of BRL 43694 significantly increased the time spent by gerbils in the social activity "attend", and acts of social investigation involving physical contact between animals were significantly increased only by the highest dose of 1 mg/kg, as was occurrence of the specific element, "groom". The duration of flight was increased in gerbils receiving the drugs at 1.5 micrograms/kg. The treatment had no effect upon seizure susceptibility or severity. It is suggested that BRL 43694 increases the sensitivity of gerbils to their social environment. At the lower dose this was seen as an increase in flight, at all doses it was associated with increase of the social activity "attend" and at the high dose it was manifested as an increase in active social interaction. Further investigations are required to assess the relevance of these findings to the purported anxiolytic activity of 5-HT3 receptor antagonists.
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PMID:Chronic administration of the 5-HT3 receptor antagonist BRL 43694; effects on reflex epilepsy and social behaviour of the Mongolian gerbil. 216 51

The 5-HT3 receptor antagonists, BRL 43694 and ICS 205-930, were each given for 21 days in the drinking fluid at 1.3 mg/l (120 micrograms/kg daily), to Mongolian gerbils, while the controls received tap water to drink. Effects of the treatments in reducing aversion to a brightly lit environment were assessed on behaviour during social encounters with an unfamiliar untreated resident, under bright white light and in a two-compartment black and white test box, after 12-16 days of treatment. Effects on behaviour under dim red illumination, when encountering unfamiliar untreated residents, were examined after 17-19 days. Behaviour during social encounters was recorded by ethological procedures. During encounters under bright white light, the frequency and duration of the social element "attend" were increased by BRL 43694 and ICS 205-930 and the frequency of "nose" was increased by BRL 43694. In the light-dark box, BRL 43694, though not ICS 205-930, reduced the time spent in the dark compartment. Under dim red light, BRL 43694 and ICS 205-930 increased the occurrence of the social elements, "sniff", "follow" and "sniff chin", suggesting increased sensitivity to olfactory stimuli. Increases of social investigation were associated with compensatory changes to non-social behaviour. It is suggested that 5-HT3 receptor antagonists may, on the one hand, increase sensitivity to social stimuli under dim red illumination and, on the other hand, show an apparent anxiolytic potential, associated with increase of other elements of social investigation under the more aversive test conditions of bright white light.
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PMID:Behavioural effects in gerbils of the 5-HT3 receptor antagonists, BRL 43694 and ICS 205-930, under circumstances of high and low light intensity. 216 21

The review presents evidence that 5-HT3 receptors within the brain may contribute to the control of behavior. 5-HT3 receptor antagonists GR38032F, zacopride, ICS 205-930 and other agents are very potent in reducing mesolimbic dopamine hyperactivity caused by the injection of amphetamine or infusion of dopamine into the rat nucleus accumbens and amygdala, and the ventral striatum of the marmoset. Such actions are distinguished from those of neuroleptic agents by a failure to reduce normal levels of activity or to induce a rebound hyperactivity after discontinuation of treatment. Indeed, the 5-HT3 receptor antagonists can prevent the neuroleptic-induced rebound hyperactivity. Further evidence that 5-HT3 receptors moderate limbic dopamine function is shown by their ability to reduce both the behavioral hyperactivity and changes in limbic dopamine metabolism caused by DiMe-C7 injection into the ventral tegmental area. The 5-HT3 receptor antagonists also have an anxiolytic profile in the social interaction test in the rat, the light/dark exploration test in the mouse, the marmoset human threat test and behavioral observations in the cynomolgus monkey. They differ from the benzodiazepines by an absence of effect in the rat water lick conflict test and a withdrawal syndrome. Importantly, the 5-HT3 receptor antagonists are highly effective to prevent the behavioral syndrome following withdrawal from treatment with diazepam, nicotine, cocaine and alcohol. Intracerebral injection techniques in the mouse indicate that the dorsal raphe nucleus and amygdala may be important sites of 5-HT3 receptor antagonist action to inhibit aversive behavior. Studies with GR38032F indicate an additional effect in reducing alcohol consumption in the marmoset. The identification and distribution of 5-HT3 receptors in the brain using a number of 5-HT3 receptor ligands, [3H]65630, [3H]zacopride and [3H]ICS 205-930 correlates between studies, and the 5-HT3 recognition sites in cortical, limbic and other areas meet the criteria for 5-HT3 receptors to mediate the above behavioral effects. Thus the use of 5-HT3 receptor antagonists reveals an important role for 5-hydroxytryptamine in the control of disturbed behavior in the absence of effect on normal behavior. The profile of action of the 5-HT3 receptor antagonists has generated a major clinical interest in their potential use for schizophrenia, anxiety and in the control of drug abuse.
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PMID:The psychopharmacology of 5-HT3 receptors. 220 69

Two 5-HT3 receptor antagonists, tropisetron (1 and 10 ng) and ondansetron (10 and 100 ng) were tested for effects on ethanol drinking in Wistar male rats after bilateral microinjection into the amygdala. The animals had limited access (2 h/day) to the 10% (v/v) ethanol solution, food and water were available ad lib during the scheduled access period. Both drugs caused a decrease in ethanol drinking. Tropisetron (1 and 10 ng) decreased ethanol intake during the first hour of access. The lower dose (10 ng) of ondansetron was more effective than the higher (100 ng) dose. The finding implicates amygdaloid 5-HT3 receptors in the mechanism of ethanol intake in Wistar rats.
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PMID:Evidence that the amygdala is involved in the inhibitory effects of 5-HT3 receptor antagonists on alcohol drinking in rats. 754 38

The effect of the 5-HT3 antagonist ondansetron on ethanol self-administration was examined in a limited access paradigm. Acute administration of ondansetron (0.01 and 0.1 mg/kg) reduced ethanol intake in male Wistar rats by 35%, whilst water intake was unaffected. Both a lower (0.001 mg/kg) and higher dose (1 mg/kg) of ondansetron failed to modify ethanol consumption. Ondansetron did not, however, alter the pharmacokinetic profile of an orally administered dose of ethanol (1 g/kg) over the same dose range. To examine the generality of these findings and to determine if tolerance would develop to the suppressant effects of ondansetron on ethanol intake, male C57BL/6 mice were treated with ondansetron (0.001, 0.01 and 0.1 mg/kg) over 22 days, 30 min prior to scheduled access to ethanol. Both 0.01 and 0.1 mg/kg doses reduced ethanol intake; however, water intake was not altered by either dose. This finding confirms and extends the generality of the effects of 5-HT3 receptor antagonists on ethanol intake across different species and different paradigms of ethanol consumption. More importantly, the present study shows that the reduction in ethanol intake induced by ondansetron was maintained even after a prolonged period of treatment and is not due to an alteration in the absorption or metabolism of ethanol.
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PMID:Effect of the 5-HT3 antagonist ondansetron on voluntary ethanol intake in rats and mice maintained on a limited access procedure. 760 51

We wished to determine if visceral perception in the rectum and stomach is altered in patients with irritable bowel syndrome and to evaluate the effects on visceral sensation of 5-HT3 receptor blockade. Twelve community patients with diarrhea-predominant irritable bowel syndrome and 10 healthy controls were studied in a double-blind, randomized, placebo-controlled study. Using two barostats, the stomach and rectum were distended, with pressure increments of 4 mm Hg, from 10 to 26 mm Hg; visceral perception was measured on an ordinal scale of 0-10. Personality traits were measured using standard psychological methods, and somatic pain was evaluated by immersion of the nondominant hand in cold water. The effect of 5-HT3 antagonism was tested with a single intravenous dose of ondansetron at 0.15 mg/kg. Gastric perception was higher in irritable bowel syndrome, but rectal distension was perceived similarly in irritable bowel syndrome and controls. Pain tolerance to cold water was also similar in irritable bowel syndrome and controls. Ondansetron induced rectal relaxation and increased rectal compliance but did not significantly alter gastric compliance or visceral perception. Psychological test scores were similar in patients and controls. We conclude that in this group of psychologically normal patients with irritable bowel syndrome, who were not chronic health-care seekers, visceral perception was normal. Ondansetron did not alter gut perception in health or in irritable bowel syndrome.
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PMID:Visceral perception in irritable bowel syndrome. Rectal and gastric responses to distension and serotonin type 3 antagonism. 772 Apr 76

Exposure of sensitised intestine to specific allergen is known to produce appreciable reduction in water and electrolyte absorption. The mediators participating in this process have not been fully characterised. The effects of the 5-hydroxytryptamine2 (5-HT2) and 5-HT3 receptor antagonists, ketanserin and granisetron, respectively, on water movement during intestinal anaphylaxis were studied. Hooded Lister rats (120-150 g) were sensitised to ovalbumen and 14 days later, intestinal water and electrolyte movement was assessed at 10 minute intervals by in situ jejunal perfusion with a plasma electrolyte solution (PES) or PES containing 20 mg/l ovalbumen. Within 20 minutes of exposure to PES+ovalbumen, net water secretion that could be completely prevented by the mast cell stabilising agent doxantrazole occurred compared with absorption with PES alone (median -20 microliters/min/g (interquartile range -43 to -5), n = 11), v (107 (86 to 113), n = 10; p < 0.01). Pre-treatment with subcutaneous ketanserin 200 micrograms/kg (n = 7) or granisetron 300 micrograms/kg (n = 8) partially inhibited the secretory response to PES+ovalbumen (18 (11 to 48) and 13 (6 to 32) respectively; both p < 0.01 compared with PES+ovalbumen control). After 40 minutes perfusion with PES+ovalbumen, the changes in water movement were less pronounced 24 (-3 to 43) and neither ketanserin or granisetron had any effect (ketanserin: 48 (28 to 87), granisetron: 41 (32 to 83); NS). In all experiments, sodium and chloride movement paralleled that of water. Thus, the profound water secretion that occurs in the early stages of intestinal anaphylaxis is partly 5-HT dependent because it can be reversed by 5-HT2 and 5-HT3 receptor antagonists. Other mediators must also be involved, especially in the late phase of anaphylaxis.
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PMID:Role of 5-hydroxytryptamine in intestinal water and electrolyte movement during gut anaphylaxis. 773 63

The effects of three doses (0.003, 0.03 and 1.0 mg/kg sc) of the 5-HT3 receptor antagonist, WAY 100289, on spatial learning and memory in the water maze were examined in rats before and after ibotenate lesions to the nucleus basalis and medial septal brain regions at the source of cholinergic projections to cortex and hippocampus. The representative cholinergic nicotinic and muscarinic receptor agonists nicotine (0.1 mg/kg) and arecoline (1.0 mg/kg) were also tested for comparison. Both arecoline and nicotine improved initial acquisition in rats before lesioning, in terms of latency to find a hidden platform and accuracy of search strategy. WAY100289 did not affect the performance of normal rats significantly, apart from some non-significant trends towards improvement with the highest dose. However, in animals showing transient navigational deficits in retention and relearning after lesioning, WAY100289 improved performance at all three doses, though ameliorative effects of nicotine and arecoline were more marked also in lesioned rats. These results show that WAY100289 improved spatial learning in animals impaired after lesions to cholinergic projection nuclei, which may reflect an interaction with cholinergic transmission to enhance cognitive function. However, in the present study, WAY100289 appeared to be less effective than direct cholinergic agonists.
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PMID:The selective 5-HT3 receptor antagonist, WAY100289, enhances spatial memory in rats with ibotenate lesions of the forebrain cholinergic projection system. 777 Jun 8

The purpose of the present study was to examine the role of serotonin (5HT) in the discriminative stimulus effects of kappa opioids. Pigeons were trained to discriminate 5.6 mg/kg of the kappa opioid, U50,488, from water. During substitution tests, both U50,488 and another kappa opioid, spiradoline, produced > 80% responding on the U50,488-appropriate key. In contrast, the non-opioid compound, phencyclidine and several serotonergic compounds failed to substitute for the U50,488 discriminative stimulus across a wide range of doses. During combination tests, the selective 5HT1A agonist, 8-OH-DPAT (0.001-3.2 mg/kg), dose-dependently attenuated the discriminative stimulus effects of 5.6 mg/kg U50,488 and 3.2 mg/kg spiradoline. This effect was reversed by the 5HT1A antagonist, NAN-190 (0.01-1 mg/kg), in a dose-dependent manner. Buspirone (0.01-10 mg/kg), a 5HT1A partial agonist, also attenuated the discriminative stimulus effects of the training dose of U50,488 but ipsapirone, another 5HT1A partial agonist, did not. Ketanserin, a 5HT2 antagonist, and MDL72222, a 5HT3 antagonist, attenuated the effects of U50,488, whereas the 5HT1B,1C agonist, mCPP, and the 5HT2 agonist, DOI, did not. Depletion of 5HT with p-CPA also attenuated U50,488's discriminative stimulus effects. Taken together, the results suggest that serotonin release is an important component in the discriminative stimulus effects produced by kappa opioids; however, the effects of DOI and mCPP alone suggest that activation of post-synaptic 5HT receptors is not sufficient to produce the full spectrum of kappa opioid discriminative stimulus effects.
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PMID:Serotonin involvement in the discriminative stimulus effects of kappa opioids in pigeons. 787 Sep 36

The roles of hippocampus (HP) and the nucleus accumbens septi (NAS) in the anxiolytic activity of two 5-HT3 receptor antagonists were studied in two animal models of anxiety, in rats. Injection of tropisetron (0.005 and 0.01 microgram) or ondansetron (1.0 and 2.5 micrograms) into the hippocampus increased punished consumption of water in the Vogel conflict test. In the open field test neither 5-HT3 receptor antagonists had anxiolytic-like effects. Tropisetron (0.01 and 0.025 microgram) injected into the NAS caused a marked increase in punished drinking, while ondansetron (0.01-15.0 micrograms) had no effect. In the open field test, tropisetron (0.001, 0.005 and 0.01 microgram) and ondansetron (1.0 and 2.5 micrograms) given to the NAS increased the number of entries into the central part of the open-field, and the time spent in the central sector of the arena. Depletion of 5-HT significantly enhanced the anxiolytic-like effect of intra-NAS-injected tropisetron in the open field, at the dose of 0.005 microgram. Moreover, 5,7-DHT lesions produced a tendency to increase motor activity in tropisetron-treated rats. Both hippocampal and accumbens 5-HT3 receptors seem to contribute to the anxiolytic-like effects of 5-HT3 antagonists in the Vogel test. It also appears that this effect of 5-HT3 receptor antagonists is related to their action on postsynaptic 5-HT3 receptors within the NAS, and depends on the functional state of the 5-HT innervation ascending from the raphe nuclei. Thus, the present data add more arguments for the more specific involvement of this limbic nucleus in emotional control.
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PMID:Serotonergic innervation of the hippocampus and nucleus accumbens septi and the anxiolytic-like action of the 5-HT3 receptor antagonists. 790 95


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