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Effect of 5-HT3 antagonists and a 5-HT(1A) agonist on fluoxetine-induced conditioned gaping reactions in rats

Cheryl L Limebeer1, Devin E Litt, Linda A Parker

  • 1Department of Psychology, University of Guelph, Guelph, Ontario, Canada, N1H 2W1.

Psychopharmacology
|December 17, 2008
PubMed
Abstract

Insights

Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine can cause nausea, modeled as conditioned gaping in rats. 5-HT(1A) agonists, but not 5-HT(3) antagonists, reversed this effect, suggesting novel therapeutic targets.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • The serotonin (5-HT) system plays a crucial role in regulating nausea and vomiting.
  • Selective serotonin reuptake inhibitors (SSRIs) are known to induce nausea in clinical settings.
  • Conditioned gaping in rats is a validated animal model for nausea.

Purpose of the Study:

  • To investigate the ability of fluoxetine, a SSRI, to induce conditioned gaping in rats.
  • To evaluate the efficacy of 5-HT(3) antagonists (ondansetron, palonosetron) and a 5-HT(1A) autoreceptor agonist (8-OH-DPAT) in reversing fluoxetine-induced conditioned gaping.
  • To compare the effects of these antagonists on conditioned gaping induced by fluoxetine versus lithium chloride (LiCl).

Main Methods:

  • Rats received pairings of sucrose solution and varying doses of fluoxetine.
  • Conditioned gaping was assessed after drug-free test trials.
  • Antagonists (ondansetron, palonosetron) or agonist (8-OH-DPAT) were administered before conditioning trials.
  • Comparisons were made between fluoxetine-induced and LiCl-induced conditioned gaping.

Main Results:

  • Fluoxetine (20 mg/kg) successfully induced conditioned gaping in rats.
  • Pretreatment with 8-OH-DPAT prevented fluoxetine-induced conditioned gaping.
  • 5-HT(3) antagonists did not reverse fluoxetine-induced conditioned gaping.
  • Palonosetron attenuated LiCl-induced conditioned gaping.

Conclusions:

  • Conditioned nausea induced by SSRIs may be refractory to 5-HT(3) antagonists.
  • 5-HT(1A) autoreceptor agonists show potential in reversing SSRI-induced nausea.
  • These findings highlight differential mechanisms underlying nausea induced by different agents.

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