Effects of serotonin antagonists on motion sickness and its suppression by 8-OH-DPAT in cats

The antagonist properties of (-)propranolol, (+)propranolol, metergoline and BMY 7378 on the known effect of 8-OH-DPAT (DPAT) to decrease motion sickness in cats has been evaluated. (-)Propranolol produced a greater decrease in the antiemetic effect of DPAT than did (+)propranolol. Although metergoline produced a decrease in the antiemetic effect of DPAT, the decrease could not be clearly attributed to interactions with 5-HT(1A) receptors because metergoline alone slightly enhanced motion sickness. Depletion of 5-HT with PCPA produced a weaker, nonsignificant enhancement of motion sickness, while mesulergine had no effect. As neither nonspecific 5-HT receptor blockade with metergoline nor depletion of 5-HT mimicked the antiemetic effect of DPAT, it was concluded that DPAT acts on postsynaptic 5-HT(1A) receptors to prevent emesis. BMY 7378 alone decreased the incidence of motion sickness. A dose just below this agonist range did not decrease the effects of DPAT.