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


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.
Limebeer
Cheryl L
CL
Department of Psychology, University of Guelph, Guelph, Ontario, Canada, N1H 2W1.
Litt
Devin E
DE
Parker
Linda A
LA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000932:Antiemetics / Q000494:pharmacology* / Q000627:therapeutic use; D017660:Autoreceptors / Q000819:agonists; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D017294:Ondansetron / Q000494:pharmacology / Q000627:therapeutic use; D000077924:Palonosetron; D011812:Quinuclidines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D058825:Serotonin 5-HT1 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists
D000932:Antiemetics; D017660:Autoreceptors; D007546:Isoquinolines; D011812:Quinuclidines; D058825:Serotonin 5-HT1 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D005473:Fluoxetine; D017294:Ondansetron; D000077924:Palonosetron; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018021:Lithium Chloride