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 5-HT3 receptor antagonists, MDL72222 and ICS205-930, on cocaine- and methamphetamine-induced place preference were examined. Cocaine (0.5-4.0 mg/kg, ip) and methamphetamine (0.25-2.0 mg/kg, ip) induced a dose-dependent place preference. The cocaine (4 mg/kg)-induced place preference was blocked by both MDL72222 and ICS205-930 (0.1 mg/kg, ip). On the other hand, the dose (0.1 mg/kg) of 5-HT3 antagonists did not block the methamphetamine (2 mg/kg)-induced place preference, although a higher dose (1.0 mg/kg) of 5-HT3 receptor antagonists did block it. The difference in sensitivity may reflect a difference in attack point in dopaminergic system of these two psychostimulants. Our findings suggest that the rewarding effects of cocaine and methamphetamine may be indirectly regulated by 5-HT3 receptor; cocaine being more sensitive to 5-HT3 receptor antagonists than methamphetamine.
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PMID:5-HT3 receptor antagonists block cocaine- and methamphetamine-induced place preference. 141 29

The cloned 5-HT3 receptor from NCB-20 neuroblastoma cells was expressed in Xenopus oocytes. In these oocytes, 5-HT, the selective 5-HT3 receptor agonists, 2-methyl-5-HT and m-chlorophenylbiguanide activated an inward current which was sensitive to the specific 5-HT3 receptor antagonist LY278584. Cocaine (0.1 to 10 microM) reversibly inhibited the current activated by 1 microM 5-HT in a concentration-dependent manner. The IC50 value is 0.7 microM and the apparent Hill coefficient is 1.55. This effect of cocaine was not dependent on membrane potential. Cocaine also produced a parallel shift of the 5-HT concentration-response curve to the right and did not reduce the maximal current induced by 5-HT. In the presence of 3 microM cocaine, the EC50 value of 5-HT was increased from 3.08 microM to 6.1 microM. Other local anesthetics such as tricaine and lidocaine also inhibited the current induced by 5-HT. These results suggest that the 5-HT3 receptors expressed in Xenopus oocytes exhibit properties similar to those in sensory neurons and neuroblastoma cells and were blocked by cocaine in a competitive manner.
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PMID:Effect of cocaine on the 5-HT3 receptor-mediated ion current in Xenopus oocytes. 760 30

Application of 5-hydroxytryptamine (5-HT) to freshly isolated rat nodose ganglion neurons produced a fast inward current when measured using the whole-cell patch-clamp technique. This current was blocked by the 5-HT3 receptor antagonist MDL72222. The selective 5-HT3 receptor agonist 2-methyl-5-HT induced a similar current. Cocaine (0.1-300 microM) applied simultaneously with 5-HT (0.25-50 microM) inhibited the 5-HT-induced current. The inhibition did not appear to be voltage dependent. If cocaine was preapplied for about 30 sec, the effect of cocaine on 5-HT current was increased. Both the peak and the steady-state 5-HT current was depressed by cocaine. However, the peak current was more sensitive to cocaine than the steady-state current. The concentration-response curves of cocaine in different agonist concentrations revealed that cocaine competitively inhibited the 5-HT3 receptor-mediated current with a pA2 value of 5.8 and an apparent KD of 1.6 microM. These results suggest that in addition to the other well known mechanisms, the 5-HT3 receptor-ion channel complex is another site for cocaine action.
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PMID:Effects of cocaine on the serotonin-induced inward current in rat nodose ganglion neurons. 796 23

The effects of a 5-HT3 receptor antagonist MDL 72222 on cocaine- and amphetamine-induced increases in extracellular dopamine in the nucleus accumbens and the dorsal striatum were studied with microdialysis technique using halothane anaesthesized rats. Dopamine and its metabolites were measured by HPLC with electrochemical detection. Cocaine elevated extracellular dopamine in the nucleus accumbens and to a lesser extent in the dorsal striatum, but it did not affect dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid. Pretreatment with MDL 72222 (25-100 micrograms/kg) dose-dependently attenuated cocaine-induced elevation of dopamine in both of the nuclei studied. Amphetamine elevated extracellular dopamine and reduced DOPAC and homovanillic acid equally in the nucleus accumbens and in the dorsal striatum. MDL 72222 also attenuated the amphetamine-induced elevation of extracellular dopamine concentration in both brain areas studied, but first at a dose of 100 micrograms/kg. The different potencies of the interactions of the 5-HT3 receptor antagonist with cocaine and amphetamine could be related to the different mechanisms by which these drugs primarily elevate extracellular dopamine.
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PMID:5-HT3 receptor antagonist MDL 72222 dose-dependently attenuates cocaine- and amphetamine-induced elevations of extracellular dopamine in the nucleus accumbens and the dorsal striatum. 873 67

Transcription regulatory factors are rapidly induced in brain by a wide variety of stimuli and may be important in coordinating changes in gene expression under-lying neuronal plasticity. Using in situ hybridization, we found that acute cocaine administration (20 mg/kg, intraperitoneally (i.p.)) produced a robust induction of both c-fos and egr-1 immediate early genes. Egr-1 messenger RNA induction was highest in the caudate putamen and in the shell of the nucleus accumbens. No significant induction was noticed after injection of fluoxetine, a selective inhibitor of serotonin uptake. Cocaine-induced egr-1 and c-fos expression was substantially reduced in the brain areas from rats in which the serotonergic projections were lesioned by injection of the neurotoxin 5,7-dihydroxytryptamine and in rats that have been injected with tropisetron, an antagonist of the 5-hydroxytryptamine (5-HT3) receptor. Conversely, the 5-HT3 receptor agonist 2-methylserotonin induced the expression of these early genes in structures including the caudate putamen and nucleus accumbens.
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PMID:The serotonergic system modulates the cocaine-induced expression of the immediate early genes egr-1 and c-fos in rat brain. 966 60

Cocaine abusers remain vulnerable to drug craving and relapse for many years after abstinence is achieved. We have recently shown that ondansetron (a 5-HT3 receptor antagonist) given 3.5 h after each daily cocaine injection reverses previously established behavioral sensitization. The purpose of the present investigation was two-fold. First, as cocaine cannot be used as therapy, we examined whether pergolide (a D1/D2 receptor agonist with reduced abuse potential) and ondansetron could reverse behavioral sensitization. Second, we investigated whether these behavioral changes were associated with parallel alterations in expression levels and/or phosphorylation changes in the NR2B and GluR1 subunits of the respective NMDA and AMPA receptors. Rats were injected for 5 consecutive days with cocaine or saline followed by 9 days of withdrawal. Starting on withdrawal day 10, animals were given vehicle, pergolide/saline, or pergolide/ondansetron for 5 consecutive days. Following a second 9-day period of withdrawal, all animals were challenged with cocaine for assessment of behavioral sensitization and tissues were collected on the following day for Western blot. Sensitization was associated with increased NR2B expression in the accumbens (NAc) shell and decreased Tyr1472 phosphorylation in the NAc core, as well as increased Ser845 phosphorylation of the GluR1 subunit in prefrontal cortex, NAc core, and shell. Pergolide/ondansetron treatment, but not pergolide alone, consistently reversed both the behavioral sensitization and the associated changes in the NMDA and AMPA receptor subunits. To the extent that sensitization plays a role in chronic cocaine abuse, a combination of these clinically available drugs may be useful in treatment of the disorder.
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PMID:Reversal of cocaine-induced behavioral sensitization and associated phosphorylation of the NR2B and GluR1 subunits of the NMDA and AMPA receptors. 1679 74

Although cocaine readily induces taste aversions, little is known about the mechanisms underlying this effect. Recent work has shown that cocaine's actions on serotonin (5-HT) may be involved. To address this possibility, the present experiments examined a role of the specific 5-HT receptor, 5-HT3, in this effect given that it is implicated in a variety of behavioral effects of cocaine. This series of investigations first assessed the aversive effects of the 5-HT3 receptor antagonist tropisetron alone (Experiment 1). Specifically, in Experiment 1 male Sprague-Dawley rats were given repeated pairings of a novel saccharin solution and tropisetron (0, 0.056, 0.18 and 0.56mg/kg). Following this, a non-aversion-inducing dose of tropisetron (0.18mg/kg) was assessed for its ability to block aversions induced by a range of doses of cocaine (Experiment 2). Specifically, in Experiment 2 animals were given access to a novel saccharin solution and then injected with tropisetron (0 or 0.18mg/kg) followed by an injection of various doses of cocaine (0, 10, 18 and 32mg/kg). Cocaine induced dose-dependent taste aversions that were not blocked by tropisetron, suggesting that cocaine's aversive effects are not mediated by 5-HT, at least at this specific receptor subtype. At the intermediate dose of cocaine, aversions appeared to be potentiated, suggesting 5-HT3 may play a limiting role in cocaine's aversive effects. These data are discussed in the context of previous examinations of the roles of serotonin, dopamine, and norepinephrine in cocaine-induced aversions.
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PMID:The effects of the 5-HT3 receptor antagonist tropisetron on cocaine-induced conditioned taste aversions. 2341 34