Figure 5.

Site(s) of action implicated in the emetic or pica response induced by the ten compounds reviewed. Systemic or i.c.v. apomorphine, morphine and nicotine activate dopamine D₂ and D₃, µ (possibly µ₁) opioid and nicotinic receptors, respectively, in the area postrema (AP) (Laffan and Borison, 1957; Osinski et al., 2005; Rudd and Naylor, 1995; Wang and Borison, 1952), although the possibility of an action on the subjacent nucleus tractus solitarius (NTS) cannot be excluded by such studies. The cytotoxic drugs cisplatin and cyclophosphamide induce the local release of 5-HT from enteroendocrine cells, which activate 5-HT₃ receptors on the peripheral terminals of abdominal vagal afferents (Rudd and Andrews, 2005). Additionally, cisplatin-induced emesis (delayed phase) can be mediated by the area postrema, but the molecular mechanism is not known (Percie du Sert et al., 2009). Abdominal vagal afferents have been implicated in the mechanism by which intragastric ipecacuanha (Andrews and Davis, 1995), copper sulphate (Wang and Borison, 1951) and CCK-8 induce emesis (Lang et al., 1988), although in the case of the latter, a direct action on receptors located on the nodose ganglion (NG) or in the brain stem cannot be excluded. The site of emetic action of lithium chloride has not been investigated but the AP is required for it to induce conditioned taste aversion in the rat (Borison, 1989). A central site of action for the PDE4 inhibitor rolipram is supported by electrophysiological (Carpenter et al., 1988) and isoform distribution studies (Mori et al., 2010), but in contrast to other compounds, the effect of area postrema ablation and vagotomy have not been investigated.