ANTIEMETIC EFFECTS OF 5-HT1A AGONISTS IN THE PIGEON

Ditolyguanidine (DTG) induced a dose-dependent emetic response in pige ons, with 100% of the birds vomiting after 5.6 mg/kg. Retching and vom iting originally induced by DTG could be conditioned to the test situa tion. Both the unconditioned and conditioned emetic responses were dos e-dependently blocked by 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DP AT) and LY228729, agonists at the 5-HT1A subtype of serotonin receptor , but not by the 5-HT3 antagonist tropisetron. Higher doses (0.25-0.5 mg/kg) of tropisetron exhibited intrinsic emetic activity which could also be prevented by 8-OH-DPAT, NAN-190, a putative 5-HT1A partial ago nist, produced both an antiemetic response when administered before DT G and also attenuated the antiemetic effects of 8-OH-DPAT. Pentobarbit al blocked the conditioned, but not the unconditioned DTG-induced emes is. These results support the possibility that 5-HT1A agonists exhibit antiemetic activity against a broad range of emetic stimuli, includin g conditioned vomiting which is usually resistant to pharmacological a ttenuation.