Antagonism of the 5-HT1A receptor stimulus in a conditioned taste aversion procedure.
The conditioned taste aversion procedure in mice was used to test for blockade of the drug stimulus of the 5-HT1A receptor agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT), 1-(4-trifluoromethyl-2-pyridinyl)-4- [4-[2-oxo-1-pyrrolidinyl]butyl]piperazine (E)-2-butenedioate (Org 13011) and the 5-HT reuptake inhibitor fluoxetine. The conditioned taste aversion induced by 8-OH-DPAT (0.22 mg/kg) and Org 13011 (0.5 mg/kg) was readily blocked by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635) (0.1 mg/kg). The conditioned taste aversion induced by fluoxetine could not be antagonized by WAY-100635 nor by the 5-HT2 receptor antagonist mianserin. It is concluded that the conditioned taste aversion induced by 8-OH-DPAT or Org 13011 is mediated via 5-HT1A receptors. The results suggest that the conditioned taste aversion induced by fluoxetine is not exclusively mediated by 5-HT1A receptors nor exclusively by 5-HT2 receptors. The results also indicate that the conditioned taste aversion paradigm can be used to test for antagonism of stimulus properties of compounds.
Berendsen
H H
HH
Department of Neuropharmacology, N.V. Organon, Oss, Netherlands. H.Berendsen@organon.oss.akzonobel.nl
Broekkamp
C L
CL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004336:Drug Antagonism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013649:Taste / Q000187:drug effects*
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide