Comparison of stimulus properties of fluoxetine and 5-HT receptor agonists in a conditioned taste aversion procedure

Eur J Pharmacol. 1994 Feb 21;253(1-2):83-9. doi: 10.1016/0014-2999(94)90760-9.


Pre-exposure to 5-hydroxytryptamine (5-HT) receptor agonists in conditioned taste aversion experiments was used to characterize the stimulus properties of fluoxetine. The taste aversion induced by fluoxetine (10 mg/kg) was completely prevented when mice were pre-exposed to fluoxetine or when they were pre-exposed to the preferential 5-HT1C receptor agonist MK 212. Pre-exposure to MK 212 also prevented the conditioned taste aversion induced by another serotonin uptake inhibitor, paroxetine. A partial attenuation of fluoxetine-induced conditioned taste aversion was seen after pre-exposure to a high dose of the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 1 mg/kg), but not to lower doses. No familiarization for the fluoxetine stimulus was obtained by pre-exposure to treatments with the mixed 5-HT1C/2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). With the reversed sequence, pre-exposure to fluoxetine prevented the conditioned taste aversion induced by MK 212 or 8-OH-DPAT and reduced that induced by DOI. It is concluded that the acute stimulus properties of fluoxetine mostly resemble those of a 5-HT1C receptor agonist. This supports the suggestion that the 5-HT1C receptor can play an important role in the therapeutic effect of 5-HT reuptake inhibitors.

Publication types

  • Comparative Study

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Amphetamines / pharmacology
  • Analysis of Variance
  • Animals
  • Avoidance Learning / drug effects*
  • Conditioning, Classical / drug effects*
  • Fluoxetine / pharmacology*
  • Male
  • Mice
  • Paroxetine / pharmacology
  • Pyrazines / pharmacology
  • Serotonin Receptor Agonists / pharmacology*
  • Taste*


  • Amphetamines
  • Pyrazines
  • Serotonin Receptor Agonists
  • Fluoxetine
  • Paroxetine
  • 6-chloro-2-(1-piperazinyl)pyrazine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • 4-iodo-2,5-dimethoxyphenylisopropylamine