The 5-HT1A agonist 8-OH-DPAT reverses the suppression of breathing but not swallowing caused by opioid administration in female rats

Abstract

The objective of our study was to determine the role of 5-HT1A receptors in modulating breathing and swallowing following opioid administration. Our previous experiments in anesthetized male and female Sprague Dawley rats demonstrated that swallow is suppressed by the opioid buprenorphine, and that female rats are more susceptible to buprenorphine-induced respiratory arrest (71% mortality at 0.3 mg/kg) than male rats (100% survival at 0.3 mg/kg). We hypothesized that following buprenorphine administration, intravenous administration of the 5-HT1A agonist 8-OH-DPAT would restore breathing and swallowing. Experiments were performed in spontaneously breathing female Sprague Dawley rats anesthetized with sodium pentobarbital ( n = 7). Bipolar electromyography (EMG) wires were inserted into various muscles to measure breathing and airway protective behaviors. Swallow was stimulated by oral water infusion. Intravenous buprenorphine was administered in doses that yield respiratory arrest in female rats. Sustained apnea occurred in 86% of animals following buprenorphine administration (one animal resisted respiratory depression). 8-OH-DPAT was then administered to effect (100, 300, or 1,000 μg/kg i.v.). 8-OH-DPAT did not restore swallow, but breathing was recovered in 100% of animals (33% at 100 μg/kg, 50% at 300 μg/kg, and 17% at 1,000 μg/kg). This effect of 8-OH-DPAT was reversed by the 5-HT1A antagonist WAY 100635 (1 mg/kg i.v.), which abolished breathing in all animals. These results indicate that 5-HT1A agonists may be utilized to restore breathing following respiratory arrest, and that opioid-induced depression of breathing and swallowing are mediated by potentially separate mechanisms. This work was supported by NIH grants HL 111215, HL 103415 and OT20D001983, the Craig H. Neilsen Foundation Pilot Research Grant 546714, Kentucky Spinal Cord and Head Injury Research Trust, and the Commonwealth of Kentucky Challenge for Excellence. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.