• The effect of serotonin and serotonin receptor antagonists on motion sickness in Suncus murinus.

      Naylor, Robert J.; Javid, Farideh A. (2002)
      In the present study, we investigated the effect of 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists and antagonists on motion sickness in Suncus murinus, and the possibility that the emetic stimulus of 5-HT can alter the sensitivity of the animals to the different emetic stimulus of motion sickness. 5-HT (1.0, 2.0, 4.0 and 8.0 mg/kg ip) induced emesis and that was antagonised by methysergide (1.0 mg/kg ip), the 5-HT4receptor antagonist sulphamate[1-[2-[(methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-methoxy-1H-indole-3-carboxylate (GR125487D; 1.0 mg/kg ip) and granisetron (0.5 mg/kg ip). Pretreatment with 5-HT caused a dose-related attenuation of the emetic response induced by a subsequent motion stimulus, which was not significantly modified by methysergide, granisetron or GR125487D pretreatment. (+)-1-(2,5-Dimethoxy-4-iodophenyl)-2-amino-propane (DOI; 0.5 and 1.0 mg/kg ip), 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg/kg ip) but not methysergide, GR125487D or granisetron, attenuated motion-induced emesis, and that was not affected by pretreatment with ketanserin (2.0 mg/kg, ip) or N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)cyclohexanecarboxamide trihydrocholoride (WAY-100635; 1.0 mg/kg ip), respectively. Indeed, ketanserin alone (0.1, 0.3, 1.0 and 2.0 mg/kg ip) attenuated motion sickness. These data indicate that 5-HT1/2, 5-HT3 and 5-HT4 receptors are involved in the induction of 5-HT-induced emesis. However, agonist action at the 5-HT1A/7 and 5-HT2 receptors, and antagonist action at the 5-HT2A receptors can attenuate motion sickness in S. murinus.
    • The effect of the 5-HT1A receptor agonist, 8-OH-DPAT, on motion-induced emesis in Suncus murinus.

      Javid, Farideh A.; Naylor, Robert J. (2006)
      In the present study we evaluated the role of 5-HT1A receptors in mediating the inhibitory action of 8-OH-DPAT, a 5-HT1A receptor agonist, in motion sickness in Suncus murinus. 8-OH-DPAT (0.1 mg/kg, i. p) attenuated motion-induced emesis which was associated with an increase in the latency of the onset to the first emetic episode. Pre-treatment with methysergide (a 5-HT1/2/7 receptor antagonist, 1.0 mg/kg, i. p.), WAY-100635 (a 5-HT1A receptor antagonist, 1.0 mg/kg, i. p.), SB269970A (a 5-HT7 receptor antagonist, 1.0 and 5.0 mg/kg, i. p.), ondansetron (a 5-HT3 receptor antagonist, 1.0 mg/kg, i. p) or GR13808 (a 5-HT4 receptor antagonist, 0.5 mg/kg, i. p) failed to modify the inhibitory action of 8-OH-DPAT on motion sickness. Furthermore, the application of either methysergide, WAY-100635, SB269970A, ondansetron or GR13808 alone had no effect on motion sickness in its own right. These data indicate that neither 5-HT1A nor any 5-HT2 receptor subtypes, 5-HT3, 5-HT4 and 5-HT7 receptors are likely to be involved in the inhibition of motion-induced emesis mediated by 8-OH-DPAT.
    • Opioid receptor involvement in the adaptation to motion sickness in Suncus murinus.

      Javid, Farideh A.; Naylor, Robert J. (2001)
      The aim of the present study was to investigate an opioid receptor involvement in the adaptation response to motion sickness in Suncus murinus. Different groups of animals were treated intraperitoneally with either saline, morphine (0.1 and 1.0 mg/kg), naloxone (1.0, 10.0 and 5.0 mg/kg) or a combination of naloxone plus morphine in the absence or 30 min prior to a horizontal motion stimulus of I Hz and 40 mm amplitude. For the study of adaptation, different groups received saline on the first trial, and in subsequent trials (every 2 days) they received either saline, naloxone (1.0 and 10.0 mg/kg, ip) or morphine (0.1 mg/kg, ip) 30 min prior to the motion stimulus. Pretreatment with morphine caused a dose-related reduction in emesis induced by a single challenge to a motion stimulus. Pretreatment with naloxone alone did not induce emesis in its own right nor did it modify emesis induced by a single challenge to a motion stimulus. However, pretreatment with naloxone (5.0 mg/kg, ip) revealed an emetic response to morphine (P<.001) (1.0 mg/kg, ip) and antagonised the reduction of motion sickness induced by morphine. In animals that received saline or naloxone (1.0 mg/kg), a motion stimulus inducing emesis decreased the responsiveness of animals to a second and subsequent motion stimulus challenge when applied every 2 days for 11 trials. However, the animals receiving naloxone 10.0 mg/kg prior to the second and subsequent challenges showed no significant reduction in the intensity of emesis compared to the first trial. The data are revealing of an emetic potential of morphine when administered in the presence of a naloxone pretreatment. The administration of naloxone is also revealing of an additional inhibitory opioid system whose activation by endogenous opioid(s) may play a role in the adaptation to motion sickness on repeated challenge in S. murinus.