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bioRxiv · 10.1101/2024.10.17.618743

Systemic CGRP and PACAP-38's Effects on Motion-Induced Nausea and Balance Behaviors in C57BL/6J Mice: A Comparison

Rahman, S. M.·Dweh, A.·Luebke, A. E.
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Abstract

Pituitary adenylate-cyclase-activating polypeptide (PACAP), particularly its dominant isoform PACAP-38, is implicated in migraine and represents a promising therapeutic target. We investigated if intraperitoneally delivered (IP) PACAP-38 impacts motion-induced nausea, postural sway, and imbalance in C57BL/6J wildtype mice using the motion-induced thermoregulation, center of pressure (CoP), rotarod, and balance beam assays. We also assessed systemic Calcitonin Gene-Related Peptides (CGRP) effects on these behaviors in parallel. Our findings indicate that IP PACAP-38 significantly disrupts motion-induced thermoregulation in mice, with notable blunting of tail vasodilation responses in both sexes. Additionally, PACAP-38 administration increased postural sway in female mice only and caused balance beam imbalances. Contrary to IP CGRP, IP PACAP-38 did not affect rotarod performance when mice were trained on a dowel with 1.5 cm radius. Our findings provide preclinical evidence supporting a potential role of PACAP-38 in vestibular migraine pathophysiology. Future research will explore if PACAP antagonism can protect against PACAP-38s effects on nausea and balance behaviors, relevant to treatment of vestibular migraine (VM), especially for patients unresponsive to triptans or CGRP-targeting therapies.

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Rahman, S. M., Dweh, A., Luebke, A. E.. 2024-10-21. Systemic CGRP and PACAP-38's Effects on Motion-Induced Nausea and Balance Behaviors in C57BL/6J Mice: A Comparison. https://doi.org/10.1101/2024.10.17.618743

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