Role of the chemoreceptor trigger zone in histamine‐induced emesis

Abstract

. In unanaesthetized dogs, the emetic action of histamine was studied after its injection into the cerebral venricles through chronically implanted cannulae in order to elucidate the role of the chemoreceptor trigger zone (CT‐zone), situated in the area postrema, for this emesis. . On injection into the lateral cerebral ventricle, about 10 times larger doses of histamine (3 mg) were required regularly to produce emesis, and it occurred after a longer latency than on injection into the fourth ventricle. This is in accord with an action of histamine on the CT‐zone. . After bilateral ablation of the CT‐zone, intraventricular injections of histamine no longer produced emesis even when injected in doses which were three to four times greater than those which regularly elicited vomiting in dogs with intact CT‐zone. The emesis produced in dogs by intraventricular injections of histamine is thus fully accounted for by an action on the CT‐zone. . Injections of chlorpromazine intramuscularly or of the two antihistamines cyclizine and mepyramine, either intramuscularly or into the lateral ventricle, prevented the emesis caused by histamine injected into the lateral ventricle. This protective action of the antihistamines—which did not extend to the emesis produced by oral copper sulphate—suggests the presence of histaminergic receptors in the CT‐zone.

Enkephalin Receptors in the Emetic Chemoreceptor Trigger Zone of the Dog

“…We believe that morphine induces emesis by an action on the enkephalin receptors in the emetic trigger zone and apomorphine may be acting on dopamine receptors in the CTZ. There is already evidence in support of histamine receptors in the chemoreceptor trigger zone (Bhargava & Dixit, 1968;Bhargava, Dixit & Palit, 1976). Thus, there may be a variety of receptors in the CTZ.…”

“…Chronic implantation of a metal cannula into either a lateral cerebral ventricle or into the IVth ventricle was performed aseptically under pentobarbitone sodium anaesthesia, according to the method described by Bhargava & Dixit (1968). The correct placement of cannula was ascertained by withdrawal of clear cerebrospinal fluid from the cannula, by a postive emetic response to an injection of apomorphine into the cannulated lateral (2 jg) or IVth ventricle (0.5 jig) 3 to 4 days after the implantation and, finally, on autopsy.…”

Nature of Histamine Receptors in the Emetic Chemoreceptor Trigger Zone

“…Although it has been proposed that histamine receptors in the ECT zone of the area postrema of the dog may fully account for the emesis induced by intraventricular histamine (Bhargava & Dixit, 1968), the nature of these receptors was not known. The present study has clearly shown the importance of both H1-and H2-receptors in the emetic action of centrally administered histamine.…”

“…The area postrema is very rich in biogenic amines, including histamine (Adam, 1961) but their precise role in the emetic chemoreceptor trigger (ECT) zone is not known. However, intraventricular administration of histamine in dogs elicited emesis which was completely blocked after surgical ablation of the ECT zone (Bhargava & Dixit, 1968 …”

Evidence for a Motion Sickness Agent in Cerebrospinal Fluid

“…Dopa mine and L-dopa [Lotti and Clark, 1974], histamine [Bhargava and Dixit, 1968] and metenkephalin [Bhargava et al, 1981] are among these putative candidates. Experi ments are needed to track concentrations of these elements and others in the CSF during the motion sickness process.…”