Abstract
Ditolyguanidine (DTG) induced a dose-dependent emetic response in pigeons, with 100% of the birds vomiting after 5.6 mg/kg. Retching and vomiting originally induced by DTG could be conditioned to the test situation. Both the unconditioned and conditioned emetic responses were dose-dependently blocked by 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT) and LY228729, agonists at the 5-HT 1A subtype of serotonin receptor, but not by the 5-HT 3 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-HT 1A partial agonist, produced both an antiemetic response when administered before DTG and also attenuated the antiemetic effects of 8-OH-DPAT. Pentobarbital blocked the conditioned, but not the unconditioned DTG-induced emesis. These results support the possibility that 5-HT 1A agonists exhibit antiemetic activity against a broad range of emetic stimuli, including conditioned vomiting which is usually resistant to pharmacological attenuation.
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