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

Abstract

RATIONALE:

The effect of manipulation of the serotonin (5-HT) system on conditioned gaping (presumably reflective of nausea in rats) was evaluated.

OBJECTIVE:

The potential of the selective serotonin reuptake inhibitor (SSRI), fluoxetine (which produces nausea in the clinic), to produce conditioned gaping in rats and of the 5-HT(3) antagonists (ondansetron and palonosetron) and the 5-HT(1A) autoreceptor agonist (8-OH-DPAT) to reverse this effect were evaluated.

MATERIALS AND METHODS:

In each of four experiments, rats received three pairings of intraorally delivered 17% sucrose solution and fluoxetine (0, 2, 10 or 20 mg/kg) and 72 h later were given a drug-free test trial. In experiment 2, rats were pretreated with the 5-HT(3) antagonists, ondansetron (0, 0.1 or 1.0 mg/kg) or the longer acting palonosetron (0.1 mg/kg), 30 min before each of three sucrose-fluoxetine (20 mg/kg) pairings. In experiment 3, rats were injected with palonosetron (0.1 mg/kg) 2 h before each of three sucrose-fluoxetine (20 mg/kg) or sucrose-lithium chloride (LiCl, 25 mg/kg) pairings. In experiment 4, rats were pretreated with the 5-HT(1A) autoreceptor agonist, 8-OH-DPAT (DPAT, 0.1 mg/kg) 30 min before each of three sucrose-fluoxetine (20 mg/kg) pairings.

RESULTS:

After two sucrose-fluoxetine pairings, the highest dose of fluoxetine tested (20 mg/kg) produced conditioned gaping reactions. These conditioned gaping reactions were prevented by pretreatment with DPAT, but not with the 5-HT(3) antagonists. On the other hand, palonosetron administered 2 h prior to sucrose-LiCl pairings attenuated conditioned gaping reactions.

CONCLUSIONS:

These results suggest that the conditioned nausea produced by SSRIs, but not LiCl, may be resistant to treatment with 5-HT(3) antagonists, but not 5-HT(1A) autoreceptor agonists.

• Authors: Cheryl L Limebeer, Devin E Litt, Linda A Parker
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 203 Issue 4 Pg. 763-70 (May 2009) ISSN: 1432-2072 [Electronic] Germany
• PMID: 19082581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiemetics
• Autoreceptors
• Isoquinolines
• Quinuclidines
• Serotonin 5-HT1 Receptor Agonists
• Serotonin 5-HT3 Receptor Antagonists
• Fluoxetine
• Ondansetron
• Palonosetron
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Lithium Chloride

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (pharmacology, therapeutic use)
• Animals
• Antiemetics (pharmacology, therapeutic use)
• Autoreceptors (agonists)
• Conditioning, Psychological (drug effects)
• Dose-Response Relationship, Drug
• Fluoxetine (pharmacology)
• Isoquinolines (pharmacology, therapeutic use)
• Lithium Chloride (pharmacology)
• Male
• Nausea (chemically induced, prevention & control)
• Ondansetron (pharmacology, therapeutic use)
• Palonosetron
• Quinuclidines (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Serotonin 5-HT1 Receptor Agonists
• Serotonin 5-HT3 Receptor Antagonists