Behavioral and electrophysiological studies of peptide-induced emesis in dogs.
The electrophysiological responses of neurons in the canine area postrema (AP) to ionophoretic application of neuropeptides and transmitters were studied and correlated with the presence or absence of an emetic response on systemic administration. Of 17 common neuropeptides 11 were emetic when applied systemically at doses of 0.03-0.35 mg/kg. The emesis was dose dependent and was no longer observed in animals with chronic ablation of the AP. The responses of 122 AP single units were recorded. Neurons were silent at rest, and most were excited by glutamate, apomorphine, and dopamine. Excitatory responses to each of eight emetic peptides were recorded in 22-65% of cells studied; no responses were found to two peptides that were not emetic. The response to glutamate was always a brief, high-frequency discharge; the responses to all 13 other excitatory substances were of long latency, low frequency, and long duration. With high ionophoretic current or multiple applications, units would frequently become spontaneously active for many minutes or longer. The similarity of response of so many substances on small neurons suggests a common ionic or metabolic mechanism underlying the response. The direct correlation between the occurrence of emesis on systemic administration and the presence of excitatory receptors on AP neurons provides strong support for the proposed role of the AP as the chemoreceptor trigger zone for emesis.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002552:Cerebral Ventricles / Q000503:physiopathology*; D004285:Dogs; D004639:Emetics / Q000494:pharmacology; D005755:Gastrins / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D008526:Medulla Oblongata / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014839:Vomiting / Q000503:physiopathology*
D004639:Emetics; D005755:Gastrins; D005971:Glutamates; D018698:Glutamic Acid; D013973:Thyrotropin-Releasing Hormone; D009638:Norepinephrine