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)

We have investigated the behavioral effect of the 5-hydroxytryptamine3 (5-HT3) receptor agonists 1-phenylbiguanide (PBG) and m-chlorophenylbiguanide (mCPBG) in rats after i.p. and i.c.v. injection. It was hoped that this approach may provide an alternative means of studying the role of 5-HT3 receptors on animal behavior, for the majority of related studies have used antagonists at this subtype. Both PBG (3-60 mg/kg, i.p.) and mCPBG (1-30 mg/kg i.p.) produced abdominal constrictions, writhing and salivation in some, but not all, rats. The most marked behaviors were seen after mCPBG (30 mg/kg, i.p.), where paw shakes and chin rubbing was also recorded. Almost certainly as a consequence of these behaviors, PBG (3-30 mg/kg, i.p.) and mCPBG (0.3-10 mg/kg, i.p.) produced a conditioned place aversion. Pretreatment with the 5-HT3 antagonists ondansetron (0.01-0.1 mg/kg, s.c.), ICS205-930 and quaternized ICS205-930 (both 0.1 mg/kg, i.p.) blocked the PBG (30 mg/kg, i.p.)-induced place aversion. PBG (30 mg/kg, i.p.) and mCPBG (10 mg/kg, i.p.) also produced a conditioned taste aversion. The central administration of PBG (1-30 micrograms, i.c.v.) and mCPBG (0.1-10 micrograms, i.c.v.) enhanced locomotor- and gnawing-related behavior, although the effects with PBG seemed more consistent. These PBG (10 micrograms, i.c.v.)-induced behaviors were completely blocked by haloperidol (0.01-0.1 mg/kg, s.c.). In contrast, ondansetron (0.0001-1 mg/kg, s.c.) and ICS205-930 (0.1 mg/kg, i.p.) produced only a mild and inconsistent attenuation of these responses. PBG (1-30 micrograms, i.c.v.) failed to produce any place conditioning (i.e., neither a preference nor aversion was found). It is concluded that activation of peripheral 5-HT3 receptors leads to aversive-type behaviors, which may be related to gastrointestinal discomfort or malaise. In contrast, central injection of PBG and mCPBG produced a range of dopamine-related behaviors; however, a 5-HT3 receptor involvement is unclear. Because both PBG and mCPBG have dopamine releasing properties, the use of 5-HT3 agonists lacking such effects and/or the use of more discrete microinjection studies are needed to more clearly elucidate the roles of 5-HT3 receptors in the central nervous system.
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PMID:Behavioral effects of the 5-hydroxytryptamine3 receptor agonists 1-phenylbiguanide and m-chlorophenylbiguanide in rats. 845 Apr 78

This study aimed to dissect the mechanisms involved in malaise induced by the anti-cancer drug cisplatin by attempting to uncouple its effects on locomotor activity, arguably at least partly indicative of fatigue, from those effects indicative of emesis (pica, gastric stasis, reduced food intake) using pharmacological agents in the rat. Over 2 days cisplatin (6 mg/kg i.p.) reduced food intake, stimulated kaolin consumption, increased the wet weight of gastric contents and reduced locomotor activity. In animals treated with cisplatin: the 5-HT3 receptor antagonist ondansetron (1 mg/kg s.c. bd.) had no effect on either activity or weight of gastric contents but did increase food intake on day 1 (P<0.05) and the total over both days (27.6+/-1.8 vs. 19.9+/-2.3g, P<0.05), reducing kaolin consumption on day 2 (P<0.01) but not the total over both days; the NK1 receptor antagonist GR205171 (1 mg/kg s.c. bd.) was without effect on activity, but reduced the wet weight of gastric contents (P<0.05), increased food intake on day 2 (P<0.01) and total consumption over both days (28.1+/-1.7 g vs. 19.9+/-2.3 g; P<0.05) and reduced kaolin consumption on day 2 (P<0.05) but not over both days; dexamethasone (2 mg/kg s.c. bd.) blocked the cisplatin-induced reduction in activity on days 1 and 2 (P<0.01), reduced the wet weight of gastric contents by 43% (P<0.01), reduced kaolin consumption on both days (P<0.01) and arguably decreased the reduction in food intake caused by cisplatin. This study has revealed novel insights into the different spectra of activities of 5-HT3 and NK1 receptor antagonists and dexamethasone, which have implications for therapeutic strategies to alleviate the emetic, anorectic, dyspeptic and activity-reducing effects of anti-cancer chemotherapy.
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PMID:Differential effects of dexamethasone, ondansetron and a tachykinin NK1 receptor antagonist (GR205171) on cisplatin-induced changes in behaviour, food intake, pica and gastric function in rats. 1714 Dec 13

Factors underlying individual vulnerability to develop alcoholism are largely unknown. In humans, the risk for alcoholism is associated with elevated cue reactivity. Recent evidence suggests that in animal models, reactivity to reward-paired cues is predictive of addictive behaviors. To model cue reactivity in mice, we used a Pavlovian approach (PA) paradigm in which mice were trained to associate a cue with delivery of a food reinforcer. We then investigated the relationship between PA status with habitual and compulsive-like ethanol seeking. After training mice to respond for 10% ethanol, habitual behavior was investigated using both an outcome devaluation paradigm, in which ethanol was devalued via association with lithium chloride-induced malaise, and a contingency degradation paradigm in which the relationship between action and outcome was disrupted. Compulsive-like behavior was investigated in a modified conditioned place preference paradigm in which footshock was paired with the reward-paired chamber. PA was found to be predictive of habitual and compulsive-like ethanol seeking. Additionally, innate risk status was related to epigenetic changes in the gene encoding the requisite subunit of the 5HT3 receptor, Htr3a, as well as 5HT3A protein expression in the amygdala. We then used pharmacological tools to demonstrate that risk status determines the ability of a 5HT3 antagonist to reduce compulsive ethanol seeking. These data indicate that risk status can be identified prior to any alcohol exposure by assessment of cue reactivity, and further that this endophenotype may be predictive of response to pharmacological treatment for components of alcoholism.
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PMID:Epigenetic and pharmacological regulation of 5HT3 receptors controls compulsive ethanol seeking in mice. 2477 65