title: Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews.
abstract: Signals from the vestibular system, area postrema, and forebrain elicit nausea and vomiting, but gastrointestinal (GI) vagal afferent input arguably plays the most prominent role in defense against food poisoning. It is difficult to determine the contribution of GI vagal afferent input on emesis because various agents (e.g., chemotherapy) often act on multiple sensory pathways. Intragastric copper sulfate (CuSO4) potentially provides a specific vagal emetic stimulus, but its actions are not well defined in musk shrews (Suncus murinus), a primary small animal model used to study emesis. The aims of the current study were 1) to investigate the effects of subdiaphragmatic vagotomy on CuSO4-induced emesis and 2) to conduct preliminary transneuronal tracing of the GI-brain pathways in musk shrews. Vagotomy failed to inhibit the number of emetic episodes produced by optimal emetic doses of CuSO4 (60 and 120 mg/kg ig), but the effects of lower doses were dependent on an intact vagus (20 and 40 mg/kg). Vagotomy also failed to affect emesis produced by motion (1 Hz, 10 min) or nicotine administration (5 mg/kg sc). Anterograde transport of the H129 strain of herpes simplex virus-1 from the ventral stomach wall identified the following brain regions as receiving inputs from vagal afferents: the nucleus of the solitary tract, area postrema, and lateral parabrachial nucleus. These data indicate that the contribution of vagal pathways to intragastric CuSO4-induced emesis is dose dependent in musk shrews. Furthermore, the current neural tracing data suggest brain stem anatomical circuits that are activated by GI signaling in the musk shrew.
authors.affiliation: Biobehavioral Medicine in Oncology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania;
authors.forename: Charles C
authors.initials: CC
authors.lastname: Horn
authors.forename: Kelly
authors.initials: K
authors.lastname: Meyers
authors.forename: Audrey
authors.initials: A
authors.lastname: Lim
authors.forename: Matthew
authors.initials: M
authors.lastname: Dye
authors.forename: Diana
authors.initials: D
authors.lastname: Pak
authors.forename: Linda
authors.initials: L
authors.lastname: Rinaman
authors.forename: Bill J
authors.initials: BJ
authors.lastname: Yates
mesh_terms: D000818:Animals; D019327:Copper Sulfate / Q000633:toxicity*; D004639:Emetics / Q000633:toxicity*; D005260:Female; D018259:Herpesvirus 1, Human / Q000145:classification / Q000502:physiology; D008297:Male; D009041:Motion Sickness; D009538:Nicotine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012788:Shrews / Q000502:physiology*; D013270:Stomach / Q000294:innervation / Q000821:virology; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*; D014839:Vomiting / Q000139:chemically induced*
chemical_list: D004639:Emetics; D009538:Nicotine; D019327:Copper Sulfate
keywords: Suncus murinus; pica; taste aversion; vagus