Mapping Neural Activities of Area Postrema and Nucleus Tractus Solitarius in Awake Rats Using Pharmacological MRI: Relevance as A Potential Biomarker for Detecting Drug-Induced Emesis
Chin C, Fox G, Hradil V, Osinski M, McGaraughty S, Skoubis P, Cox B, Luo Y
Drug-induced emesis, a major concern in patient care and drug discovery, can be triggered by neural activation at brainstem regions, including area postrema (AP) and nucleus tractus solitarius (NTS). Using CBV-based phMRI in awake rats, we imaged neural activities in AP/NTS following the administration of known emetic agents (apomorphine and ABT-594) as a potential biomarker in a species that is routinely used for efficacy studies but does not show emesis. Observed dose-related activities in AP/NTS agree with behavioral measures obtained using a ferret model at relevant plasma levels, indicating phMRI in rats has potential as a biomarker for emesis liability.