Receptor-selective agonists induce emesis and Fos expression in the brain and enteric nervous system of the least shrew (Cryptotis parva).
Research on the mechanisms of emesis has implicated multiple neurotransmitters via both central (dorsal vagal complex) and peripheral (enteric neurons and enterochromaffin cells) anatomical substrates. Taking advantage of advances in receptor-specific agonists, and utilizing Fos expression as a functional activity marker, this study demonstrates a strong, but incomplete, overlap in anatomical substrates for a variety of emetogens. We used cisplatin and specific agonists to 5-HT(3) serotonergic, D(2)/D(3) dopaminergic, and NK(1) tachykininergic receptors to induce vomiting in the least shrew (Cryptotis parva), and quantified the resulting Fos expression. The least shrew is a small mammal whose responses to emetic challenges are very similar to its human counterparts. In all cases, the enteric nervous system, nucleus of the solitary tract, and dorsal motor nucleus of the vagus demonstrated significantly increased Fos immunoreactivity (Fos-IR). However, Fos-IR induction was notably absent from the area postrema following the dopaminergic and NK(1) receptor-specific agents. Two brain nuclei not usually discussed regarding emesis, the dorsal raphe nucleus and paraventricular thalamic nucleus, also demonstrated increased emesis-related Fos-IR. Taken together, these data suggest the dorsal vagal complex is part of a common pathway for a variety of distinct emetogens, but there are central emetic substrates, both medullary and diencephalic, that can be accessed without directly stimulating the area postrema.
Ray
Andrew P
AP
Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854, USA.
Chebolu
Seetha
S
Darmani
Nissar A
NA
D000223:Adaptation, Psychological; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism; D004639:Emetics / Q000008:administration & dosage / Q000494:pharmacology*; D017615:Enteric Nervous System / Q000166:cytology / Q000378:metabolism*; D005260:Female; D007274:Injections, Intraperitoneal; D009474:Neurons / Q000378:metabolism*; D010477:Perfusion; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012788:Shrews; D017552:Solitary Nucleus / Q000166:cytology / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013997:Time Factors; D014630:Vagus Nerve / Q000166:cytology / Q000378:metabolism; D014839:Vomiting / Q000139:chemically induced* / Q000517:prevention & control
D004639:Emetics; D016760:Proto-Oncogene Proteins c-fos; D012701:Serotonin; D013373:Substance P
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