Distribution of c‐Fos Labeling Elicited by Intragastric Copper Sulfate: Comparison with Labeling Induced by Galvanic Vestibular Stimulation

Abstract

The neural pathways that produce nausea and emesis are poorly defined. Although it is widely postulated that a “final common pathway” is activated during emetic responses elicited by any stimulus, this hypothesis has not been adequately tested. In a prior study (Balaban et al., PLoS ONE 9(1): e86730, 2014) we mapped the distribution of Fos labeling in the feline brainstem elicited by galvanic vestibular stimulation (GVS) that evoked retching and other indicators of nausea. As a comparison, in the present study we mapped Fos labeling patterns induced by intragastric administration of copper sulfate (CuSO4), which produces emesis by activating vagal afferent fibers. Emetic responses slowly build‐up during GVS, but occur rapidly following CuSO4 administration. In 10 felines (6 male, 4 female), doses of CuSO4 ranging from 83 to 322 mg were administered through an intragastric catheter or gavage, and ~2 hours later animals were perfused with paraformaldehyde. The brain was sectioned and processed for Fos labeling as in our prior study (Balaban et al., PLoS ONE 9(1): e86730, 2014). Three additional animals served as controls and did not receive intragastric CuSO4. Some brainstem areas exhibited Fos labeling following either GVS or CuSO4 treatments, as shown in Fig. 1: the commissural, medial and lateral regions of nucleus tractus solitarii, lateral reticular nucleus, medullary lateral tegmental field, subtrigeminal nucleus, medullary raphe nuclei, parabrachial nucleus, and locus coeruleus. However, the labeling patterns also diverged: CuSO4 administration produced virtually no labeling in the vestibular nuclei (which was heavy following GVS), more labeling in nucleus tractus solitarii and the medullary raphe nuclei, and less labeling in the pontine raphe nuclei. These findings support the hypothesis that some brainstem areas mediate nausea and emesis induced by any stimulus, independent of how quickly the responses develop, but also suggest that unique pathways may be activated by particular emetic stimuli.