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 local application of the 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide (CPBG), and i.p. administration of ethanol on the extracellular levels of dopamine (DA) in the ventral tegmental area (VTA) were studied using in vivo microdialysis. Adult female Wistar rats were implanted with microdialysis probes in the VTA at least 24 h before each experiment. Stable extracellular levels of DA (101 +/- 9 fmol/20 min) were established before initiating the experiments. Application of 10-250 microM CPBG through the microdialysis probe dose-dependently enhanced the extracellular concentrations of DA but did not alter the levels of either 3,4-dihydroxyphenylacetic acid or homovanillic acid in the dialysate. The effects of CPBG were reversible and dependent upon Ca2+. Co-perfusion with the 5-HT3 receptor antagonist, 3-tropanyl-indole-3-carboxylate (ICS 205-930), inhibited the effects of CPBG on enhancing extracellular DA levels. The i.p. administration of 2 g/kg ethanol significantly (p < 0.005) enhanced the levels of DA to 150% of baseline values; this ethanol-induced increase was prevented by local perfusion with 100 microM ICS 205-930. These results suggest that 5-HT3 receptors in the VTA are involved in regulating the somatodendritic release of DA and in mediating the stimulatory effects of ethanol on this neuronal system.
Alcohol
PMID:Serotonin-3 receptor and ethanol-stimulated somatodendritic dopamine release. 894 51

The 5-HT2 receptor antagonist, ritanserin, reduces alcohol intake in rats and the nucleus accumbens (NAC) has been proposed as a site of action for the drug. Recent microdialysis studies have shown that acute subcutaneous (SC) administration of ritanserin increases extracellular 5-HT levels in the NAC. The present study evaluated, in genetically heterogeneous rats with developed preference for 3% ethanol, whether the attenuation of ethanol intake induced by ritanserin might be related to its effect on the synaptic availability of 5-HT in the NAC. Damaging 5-HTergic neurons by intracerebroventricular infusion of 5,7-dihydroxytryptamine (5,7-DHT) abolished the effect of ritanserin on ethanol consumption. Injections of the 5-HT3 receptor antagonist MDL 72222 into the NAC significantly reduced the inhibitory effect of SC injection of ritanserin, 1 mg/kg, and completely abolished the effect of ritanserin, 0.1 mg/kg. Subcutaneous injections of MDL 72222, 0.3 mg/kg 3 times/day, suppressed the effect of SC ritanserin, 0.1 mg/kg. The present findings, together with those of previous experiments showing that the tryptophan hydroxylase inhibitor p-chlorophenylalanine abolishes the effect of ritanserin, support the hypothesis that its effect on ethanol intake may be due to increased synaptic availability of 5-HT into the NAC.
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PMID:Possible mechanism of action for the attenuation of ethanol intake induced by ritanserin in rats. 895 79

Previous studies have shown that naltrexone and ondansetron, an opiate and 5-HT3 receptor antagonist respectively, can reduce alcohol self-administration. In the present study, we have shown a synergistic interaction between naltrexone and ondansetron in reducing alcohol intake in mice and rats. Small doses of ondansetron and naltrexone which are essentially ineffective on their own, produce powerful suppression of alcohol intake when given together. Although the exact mechanisms underlying this synergistic interaction remain to be explored, the combined use of these agents might have potential clinical importance.
Alcohol Alcohol Suppl 1994
PMID:Interaction between opiate and 5-HT3 receptor antagonists in the regulation of alcohol intake. 897 81

The present study was performed to examine the involvement of serotonin-3 (5-HT3) receptors in the rat nucleus accumbens (ACC) in alcohol dependence. In alcohol-treated rats, perfusion of 40 mM K+ and 100 mM ethanol (EtOH) through the microdialysis probe increased the extracellular levels of ACC dopamine (DA), compared with controls. Perfusion of the serotonin (5-HT) uptake inhibitor sertlarine enhanced the extracellular levels of ACC 5-HT in both groups. Increased 5-HT availability in the synaptic clefts on the ACC further activated ACC DA release in the alcohol-treated rats, in comparison with controls. In the final experiments, perfusion of the 5.0 microM 5-HT3 receptor agonist 2-methyl-5-HT (2-Me-5-HT) through the microdialysis probe enhanced the extracellular levels of ACC DA. Magnitude of 2-Me-5-HT-induced DA release was significantly higher in alcohol-treated rats than in controls. On the other hand, 40 mM K(+)- and 100 mM EtOH-induced extracellular 5-HT release in alcohol-treated rats were markedly inhibited. These results show that (1) chronic alcohol intake increases the sensitivity of 5-HT3 receptors, (2) 5-HT3 receptors regulate DA release in the ACC, (3) the dopaminergic neuronal systems associated with 5-HT3 ionophore in the ACC were upregulated after chronic alcohol exposure, and (4) chronic alcohol intake desensitizes the serotonergic neuronal systems in rat ACC. These findings suggest that neurochemical functions of 5-HT3 receptors in regulating DA release in the ACC after alcohol exposure compensate for the dysfunction of serotonergic activity to restore the original properties in processing alcohol tolerance and that the development of alcohol dependence may be mediated by ACC 5-HT3 receptors.
Alcohol Clin Exp Res 1996 Dec
PMID:Possibility of 5-HT3 receptor involvement in alcohol dependence: a microdialysis study of nucleus accumbens dopamine and serotonin release in rats with chronic alcohol consumption. 898 29

Ethanol-induced emesis were investigated using Suncus murinus and the emetogenic mechanisms of ethanol were compared with those of cisplatin. Intraperitoneal injection of ethanol caused dose-dependent emesis with ED50 value of 22.3% (v/v) when injection volume was adjusted to 4 ml/kg. Intraperitoneal and subcutaneous injection of acetaldehyde also caused dose-dependent emesis (ED50 = 3.5% (v/v) with an extremely shorter latency (6% i.p.: 1.0 +/- 0.3 min cf. 40% ethanol: 13.0 +/- 1.9 min). Neither ethanol nor acetaldehyde caused emetic responses when injected intracerebroventricularly. Pretreatment with disulfiram, an inhibitor of liver aldehyde dehydrogenase, potentiated the emetogenic effects of ethanol. Surgical abdominal vagotomy, which blocks cisplatin-induced emesis completely, did not prevent ethanol-induced emesis. 5-HT3 receptor antagonists, which also cause complete inhibition of cisplatin-induced emesis, did not affect the responses. However, ethanol-induced emesis was prevented by the pretreatment with 8-hydroxy-2-(di-n-propylamino)tetrarin hydrobromide (8-OH-DPAT) and N-(2-mercaptopropionyl)-glycine (MPG) dose-dependently. The tackykinin NK1 receptor antagonist (+)-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenyl-piperidine (CP-99,994) also attenuated ethanol-induced emesis. Taken together, these results suggest that 1) acetaldehyde is probably responsible for ethanol-induced emesis, 2) active site for ethanol maybe peripheral, 3) ethanol-induced emesis is mediated by free radicals, and 4) mechanism of ethanol-induced emesis and that caused by cisplatin are different in many respects, although in some they are similar and that the precise pathways remain to be identified. Therefore, the tolerance to emetogenic effects of cisplatin in alcoholic patients cannot be explained as a simple cross desensitization of the pathway.
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PMID:Ethanol-induced emesis in the house musk shrew, Suncus murinus. 901 Apr 80

Numerous works have demonstrated an interaction between 5-HT3 receptor antagonists and some of the effects of ethanol (EtOH) using biochemical, electrophysiological, and behavioral techniques. Thus 5-HT3 antagonists are capable of reducing EtOH-induced release of dopamine in the nucleus accumbens, EtOH-induced hyperlocomotion, and voluntary EtOH consumption in laboratory animals. In addition to its rewarding effect, EtOH possesses aversive properties as demonstrated in the conditioned taste aversion (CTA) and conditioned place aversion (CPA) paradigms. The role of 5-HT3 receptors in aversive effects of EtOH remains, however, unknown. We decided to study the effect of 5-HT3 antagonist, tropisetron, on aversive properties of EtOH (1.5 g/kg i.p.) in rats using the CTA and CPA models. In addition, effect of tropisetron on morphine (Mf)-induced CTA (10.0 mg/kg SC) was investigated. Tropisetron (0.001-0.5 mg/kg) did not influence CTA produced by EtOH and Mf. When given alone, it failed to produce any taste conditioning. Furthermore, tropisetron did not modify CPA induced by EtOH. Our results suggest that 5-HT3 receptors are not involved in aversive effects of acute doses of EtOH.
Alcohol
PMID:5-HT3 receptor antagonist, tropisetron, does not influence ethanol-induced conditioned taste aversion and conditioned place aversion. 901 26

The influence of ethanol on 5-hydroxytryptamine (5-HT)-induced tachycardia mediated by 5-HT3 receptor activation in the isolated guinea-pig atrium was studied. Ethanol at 200 mM significantly inhibited 5-HT - but not isoproterenol- or histamine-induced tachycardia in the isolated guinea-pig atrium. The same inhibitory effect was observed in response to 2-propanol and chloral hydrate application. Both 2-propanol at 100 mM and chloral hydrate at 1 mM exhibited inhibitory effects on 5-HT -induced tachycardia as potent as those of ethanol at 200 mM. These alcohols did not inhibit the tachycardia induced by isoproterenol or histamine. The inhibitory effects of the alcohols seemed to be specific for 5-HT and to increase according to their lipophilicity. Our results suggest that the inhibitory effects of ethanol on 5-HT3 receptor-mediated tachycardia are related to the direct effect of ethanol on 5-HT3 receptors in the atrium.
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PMID:Inhibitory effect of ethanol on the 5-HT3 receptor-mediated tachycardia in isolated guinea-pig atrium. 908 82

The use of ondansetron, a selective serotonin 5-HT3 receptor antagonist, is well established in patients with nausea and vomiting associated with cancer chemotherapy, radiotherapy or anaesthesia and surgery. The wide distribution of 5-HT3 receptors in the body and the role of these receptors in disease have provided the rationale for investigation of ondansetron in novel applications. Preliminary data have shown ondansetron to have clinical benefit in patients with nausea and vomiting associated with drug overdosage or poisoning, anti-infective or antidepressant therapies, uraemia or neurological trauma, and in patients with pruritus. Patients with gastrointestinal motility disorders (e.g. carcinoid syndrome, irritable bowel syndrome, diarrhoea associated with cryptosporidiosis or diabetes, and chronic refractory diarrhoea) have also shown some improvement when treated with ondansetron, as have patients with certain pain or CNS-related disorders [e.g. alcohol (ethanol) dependence, opiate withdrawal, vertigo, cerebellar tremor and Parkinson's disease treatment-related psychosis]. In contrast to conventional antiemetics, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. Furthermore, unlike dopamine receptor-blocking neuroleptics, ondansetron does not appear to worsen the symptoms of Parkinson's disease. Thus, in addition to its established indications, preliminary results suggest that ondansetron may be beneficial in a number of novel applications. This drug may represent a treatment alternative in patients with refractory disease, or an effective treatment of conditions for which current therapies are either poorly tolerated or not available. Further investigation of ondansetron in a range of potential new applications appears to be warranted.
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PMID:Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. 911 22

The effects of acute treatment with 5-HT3 receptor antagonists, ondansetron and ICS 205-930, on the stimulation of activity induced by ethanol-and cocaine were examined. Ethanol (1.8 or 2 g/kg i.p.) or cocaine (15 mg/kg i.p.) produced a significant increase in locomotor activity (LMA) in DBA/2N mice. Pretreatment with ondansetron or ICS 205-930, in doses ranging from 0.001 to 0.1 mg/kg (s.c), did not modify ethanol or cocaine induced stimulation of activity. In contrast, pretreatment with a 10 micrograms/kg dose of either SCH 23390 or spiperone, a D1 and D2 dopamine (DA) receptor antagonist respectively, completely antagonized the stimulation of LMA induced by ethanol. Similar dose of SCH23390, but not spiperone, blocked the stimulation of activity induced by cocaine. These results indicate that D1 but not D 2 DA receptors play a significant role in cocaine induced hyperactivity whereas both D1 and D2 are involved the locomotor activating effects of ethanol.
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PMID:Effects of 5-HT3, D1 and D2 receptor antagonists on ethanol- and cocaine-induced locomotion. 916 90

The present study examined the effect of ethanol (0.25-1.0 g/kg, I.P.) alone and in combination with drugs affecting different ligand-gated ion channels on a horizontal locomotor activity of male Wistar rats. None of the drugs given alone affected the locomotor activity. Similarly, combining ethanol either with nicotine (0.1 or 0.6 mg/kg, S.C.) or the competitive NMDA receptor antagonist, CGP 40116 (0.5 mg/kg, I.P.) did not result in any significant changes in ambulation. On the other hand, a significant hyperadditive interaction between ethanol (0.5 or 1.0 g/kg) and the uncompetitive NMDA receptor antagonist, dizocilpine (0.1 mg/kg, I.P.) was found. Thus, a combined administration of ethanol and dizocilpine produced a marked stimulation of the locomotor activity. Combining 1.0 g/kg ethanol with the 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide (5.0 mg/kg, I.P.) tended to produce locomotor stimulation. Our results suggest the existence of interaction between ethanol and the NMDA receptor complex in mediation of locomotor stimulation. Alternatively, a common neurotransmitter system (other than glutamatergic) mediate central stimulatory effects of ethanol and dizocilpine. A possible role of dopamine in this interaction is being discussed.
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PMID:Interactions of ethanol with nicotine, dizocilpine, CGP 40116, and 1-(m-chlorophenyl)-biguanide in rats. 940 28


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