The opioid‐induced suppression of augmented (‘sigh’) breaths is dose‐dependent and prevented by co‐administration of naloxone

Abstract

We tested whether the morphine (MOR) induced suppression of augmented breaths (ABs) can be prevented by the non‐specific, competitive opioid receptor antagonist naloxone (NX). Further we determined whether the suppression of ABs follows a dose‐response pattern in the low‐end recommended dose range. We studied breathing in 8 rats on 4 separate days, giving four dosages of MOR s.c. in randomized order: 0 mg/kg (saline control), 1, 3, and 5 mg/kg. In a second set of 8 animals, we co‐administered either {MOR (5mg/kg) + NX (5 mg/kg)}, or {MOR (5mg/kg) + saline control (1 ml/kg)} on two separate days and monitored animals for 2 hours. MOR suppressed ABs in a typical doseresponse fashion, from 6.5 ± 1.6 ABs/15mins (control) to 1.5 ± 1.5, and 0.6 ± 1.8 ABs/15mins in the 3 and 5 mg/kg dose conditions respectively (both p<0.001). 5 mg/kg MOR caused ABs to be completely eliminated in all but one of the 8 animals we studied. In the second experiment, MOR caused a rapid and potent suppression of ABs across a two‐hour monitoring interval that was prevented by NX co‐administration. There were significantly more ABs when NX was co‐administered with MOR, regardless of the time interval across the 2 hours at which they were assessed post‐injection (p<0.001). In summary, MOR suppresses ABs in a dose‐response manner in the low‐end of the recommended dosage range, and this effect occurs via typical opioid‐receptor mediated pathways.This study received financial support from the Department of Medicine, Penn State College of Medicine, in the form of laboratory start‐up funds.