Comparison of stimulus properties of fluoxetine and 5-HT receptor agonists in a conditioned taste aversion procedure.
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.
Neuropharmacology Department, Organon International B.V., Oss, Netherlands.
H H
HH
Berendsen
C L
CL
Broekkamp
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003214:Conditioning, Classical / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D017374:Paroxetine / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013649:Taste
D000662:Amphetamines; D011719:Pyrazines; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; D017374:Paroxetine; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine