Facilitatory effects of LY404187, a positive allosteric modulator of AMPA receptors, on swallowing initiation in anesthetized male rats

Objective The present study aimed to investigate the effects of the systemic administration of LY404187, a positive allosteric modulator of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), on swallowing function. Design Experiments were conducted on 68 male Sprague-Dawley rats anesthetized with urethane. Upper airway distention with continuous airflow and the topical laryngeal application of distilled water or capsaicin were used to induce swallowing, which was identified by electromyographic activity recordings from the mylohyoid and thyrohyoid muscles. We investigated the effects of systemic administration of LY404187 (0.25–5.0 mg/kg), an angiotensin-converting enzyme inhibitor (perindopril), a dopamine agonist (amantadine), or a benzodiazepine inverse agonist (S-8510) on swallowing initiation. Results An optimal concentration of LY404187 (1.0 mg/kg) significantly increased the number of airflow-induced swallows compared with before administration. However, LY404187 did not modulate the initiation of chemically induced swallows. The pre-administration of talampanel, an AMPAR antagonist, diminished facilitatory effects of LY404187 on airflow-induced swallows. Perindopril, amantadine, and S-8510 did not facilitate both mechanically and chemically induced swallows. Conclusion These results suggest that LY404187 facilitates the initiation of mechanically induced swallows via AMPAR activation.