Emesis may be modulated via multiple mechanisms. The actions of
ghrelin suggest an ability to couple an induction of hunger with preparation of the stomach for ingestion of food. Such a process might reduce any tendency to vomit, so an
anti-emetic activity of
ghrelin was investigated in the ferret
cisplatin-induced
emesis model. In controls, intra-peritoneal
cisplatin (10 mg/kg) induced 41.4+/-8.4 episodes of
emesis comprising 310.4+/-55.3 retches and 28.8+/-6.9 vomits during the 6h observation; the latency to onset of the first
emetic episode was 108.9+/-4.8 min. Intra-peritoneal
ghrelin (1mg/kg, split as a 30 min pre- and 30 min-post dose) did not induce a change in behaviour or modify
cisplatin-induced
emesis (p>0.05). Intracerebroventricular (i.c.v.) administration (third ventricle) was achieved via a pre-implanted
cannula. At the first
emetic episode following
cisplatin,
ghrelin or vehicle (20 microl saline) was administered i.c.v. During the 30 min following the initial episode of
emesis, control animals exhibited 18.0+/-2.6
emetic episodes comprising 160.3+/-24.1 retches and 13.8+/-2.7 vomits.
Ghrelin 10 microg i.c.v. reduced the number of retches by 61.5% (p<0.05) and at a dose of 30 microg i.c.v.
ghrelin reduced the number of episodes, individual retches and vomits by 74.4 (p<0.05), 80.4 (p<0.01), and 72.5% (p<0.05), respectively. At subsequent time periods there were no differences between
ghrelin- or saline-treated animals (p>0.05). An ability of
ghrelin to reduce
emesis is consistent with a role in modulating gastro-intestinal functions and identifies a novel approach to the treatment of
emesis.