DISCRIMINATIVE STIMULUS PROPERTIES OF FLESINOXAN - EFFECTS OF ENANTIOMERS, (S)-UH301 AND WAY-100635

Rats were trained to discriminate the specific 5-HT1A receptor agonist (+)-flesinoxan ioxin-5-yl)-1-piperazinyl]ethyl]-4-flurobenoamide) (1.5 mg/kg p.o.) from water in a two-fever operant procedure. Generalizati on tests were conducted with the enantiomers and racemate of flesinoxa n and the 5-HT1A receptor antagonists (S)-UH301 (S)-5-fluoro-8-hydroxy -2-(dipropylamino)-tetralin) and WAY-100635 ethoxyphenyl)-1-piperaziny l]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride). (S) -UH301, WAY-100635 and fentanyl were investigated for their antagonist ic properties. The (+)-flesinoxan stimulus generalized to (-)-flesinox an and the racemate. The ED(50) values for generalization corresponded well with the affinities of the enantiomers and the racemate for the 5-HT1A receptor. The flesinoxan cue could not be mimicked by (S)-UH301 or WAY-100635, but (S)-UH301 reduced response rates. Antagonism tests showed that both (S)-UH301 and WAY-100635 dose dependently antagonize d the flesinoxan cue, with ID50 values of 0.52 and 0.03 mg/kg s.c., re spectively. Fentanyl had no significant antagonistic properties. It is concluded that rats can learn to discriminate orally administered (+) -flesinoxan from water. The generalization of flesinoxan to the (-)-en antiomer and the antagonism of flesinoxan's cue by specific 5-HT1A rec eptor antagonists are further evidence for the involvement of flesinox an's 5-HT1A receptor agonistic properties in its discriminative stimul us effects.