DISCRIMINATIVE STIMULUS EFFECT OF FLESINOXAN - EFFECTS OF 5-HT1A ANTAGONISTS AND PCPA

Rats were trained to discriminate 0.3 mg/kg (IP) flesinoxan from salin e in a standard two-lever operant procedure and thereafter subjected t o generalization and antagonism tests with the 5-HT1A receptor agonist ipsapirone and the beta-adrenergic/5-HT1 receptor antagonist pindolol . Ipsapirone (3.0 mg/kg) completely substituted for flesinoxan. Both t he flesinoxan (0.3 mg/kg) and the ipsapirone cue (3.0 mg/kg) were dose -dependently blocked by (+/-)-pindolol. In a second group of rats, tra ined to discriminate 0.5 mg/kg (IP) of flesinoxan from saline, the put ative 5-HT1A antagonist NAN-190 (in the dose range of 1.0 to 6.0 mg/kg ) partially blocked the cue of flesinoxan. Generalization studies reve aled that the flesinoxan cue could not be mimicked by NAN-190 (3.0 mg/ kg). Finally, rats were pretreated with the 5-HT depletor parachloroph enylalanine (PCPA) and thereafter tested with the flesinoxan training dose (0.5 mg/kg). PCPA pretreatment did not significantly attenuate th e recognition of the flesinoxan cue. The present results are in agreem ent with previous findings concerning the stimulus effect of flesinoxa n and point to a mechanism that involves the activation of 5-HT1A rece ptors in the brain. Depletion of 5-HT did not significantly affect the stimulus effect of flesinoxan, suggesting that presynaptic 5-HT1A rec eptors do not play a crucial role in the mechanism underlying the stim ulus effect of flesinoxan.