Atropine facilitates water-evoked swallows via central muscarinic receptors in anesthetized rats

Am J Physiol Gastrointest Liver Physiol. 2023 Aug 1;325(2):G109-G121. doi: 10.1152/ajpgi.00039.2023. Epub 2023 May 23.

Abstract

Anticholinergic medication causes impaired swallowing with hyposalivation. However, the underlying mechanisms by which these drugs modulate the swallowing reflex remain unclear. This study investigated the effects of the muscarinic acetylcholine receptor (mAChR) nonspecific antagonist atropine on the initiation of swallowing. Experiments were performed on 124 urethane-anesthetized rats. A swallow was evoked by either topical laryngeal application of a small amount of distilled water (DW), saline, citric acid, or capsaicin; upper airway distention with a continuous airflow; electrical stimulation of the superior laryngeal nerve (SLN); or focal microinjection of N-methyl-d-aspartate (NMDA) into the lateral region of the nucleus of the solitary tract (L-nTS). Swallows were identified by electromyographic bursts of the digastric and thyrohyoid muscles. Either atropine, the peripheral mAChR antagonist methylatropine, or antagonists of mAChR subtypes M1-M5 were intravenously delivered. Atropine at a dose of 1 mg/kg increased the number of DW-evoked swallows compared with baseline and did not affect the number of swallows evoked by saline, citric acid, capsaicin, or upper airway distention. Methylatropine and M1-M5 antagonists did not significantly change the number of DW-evoked swallows. Bilateral SLN transection completely abolished DW-evoked swallows, and atropine decreased the swallowing threshold of SLN electrical stimulation. Finally, microinjection of NMDA receptor antagonist AP-5 into the L-nTS inhibited DW-evoked swallows, and atropine facilitated the initiation of swallowing evoked by NMDA microinjection into this region. These results suggest that atropine facilitates DW-evoked swallows via central mAChR actions.NEW & NOTEWORTHY Atropine facilitated the distilled water (DW)-evoked swallows in anesthetized rats. Atropine decreased the swallowing threshold evoked by electrical stimulation of the superior laryngeal nerve, which is a primary sensory nerve for the initiation of DW-evoked swallows. Atropine facilitated the swallows evoked by N-methyl-d-aspartate microinjection into the lateral region of the nucleus of the solitary tract, which is involved in the DW-evoked swallows. We speculate that atropine facilitates the DW-evoked swallows via central muscarinic receptor actions.

Keywords: atropine; distilled water; nucleus of the solitary tract; superior laryngeal nerve; swallowing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atropine Derivatives / pharmacology
  • Atropine* / pharmacology
  • Capsaicin / pharmacology
  • Citric Acid / pharmacology
  • Deglutition / physiology
  • Electric Stimulation
  • N-Methylaspartate* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic
  • Reflex / physiology
  • Water / pharmacology

Substances

  • methylatropine
  • Atropine
  • N-Methylaspartate
  • Water
  • Capsaicin
  • Atropine Derivatives
  • Receptors, Muscarinic
  • Citric Acid