Motion sickness occurs under a variety of circumstances and is common in the general population. It is usually associated with changes in gastric motility, and
hypothermia, which are argued to be
surrogate markers for
nausea; there are also reports that respiratory function is affected. As laboratory rodents are incapable of
vomiting, Suncus murinus was used to model
motion sickness and to investigate changes in gastric myoelectric activity (GMA) and temperature homeostasis using radiotelemetry, whilst also simultaneously investigating changes in respiratory function using whole body plethysmography. The
anti-emetic potential of the highly selective
histamine H1 receptor antagonists,
mepyramine (brain penetrant), and
cetirizine (non-brain penetrant), along with the
muscarinic receptor antagonist,
scopolamine, were investigated in the present study. On isolated ileal segments from Suncus murinus, both
mepyramine and
cetirizine non-competitively antagonized the contractile action of
histamine with pK b values of 7.5 and 8.4, respectively;
scopolamine competitively antagonized the contractile action of
acetylcholine with pA2 of 9.5. In responding animals, motion (1 Hz, 4 cm horizontal displacement, 10 min) increased the percentage of the power of bradygastria, and decreased the percentage power of normogastria whilst also causing
hypothermia. Animals also exhibited an increase in respiratory rate and a reduction in tidal volume.
Mepyramine (50 mg/kg, i.p.) and
scopolamine (10 mg/kg, i.p.), but not
cetirizine (10 mg/kg, i.p.), significantly antagonized motion-induced
emesis but did not reverse the motion-induced disruptions of GMA, or
hypothermia, or effects on respiration. Burst analysis of plethysmographic-derived waveforms showed
mepyramine also had increased the inter-retch+vomit frequency, and
emetic episode duration. Immunohistochemistry demonstrated that motion alone did not induce c-fos expression in the brain. Paradoxically,
mepyramine increased c-fos in brain areas regulating
emesis control, and caused
hypothermia; it also appeared to cause sedation and reduced the dominant frequency of slow waves. In conclusion, motion-induced
emesis was associated with a disruption of GMA, respiration, and
hypothermia.
Mepyramine was a more efficacious
anti-emetic than
cetirizine, suggesting an important role of centrally-located
H1 receptors. The ability of
mepyramine to elevate c-fos provides a new perspective on how
H1 receptors are involved in mechanisms of
emesis control.