Buprenorphine differentially alters breathing among four congenic mouse lines as a function of dose, sex, and leptin status

Abstract

The opioid buprenorphine alters breathing and the cytokine leptin stimulates breathing. Obesity increases the risk for respiratory disorders and can lead to leptin resistance. This study tested the hypothesis that buprenorphine causes dose-dependent changes in breathing that vary as a function of obesity, leptin status, and sex. Breathing measures were acquired from four congenic mouse lines: female and male wild type C57BL/6J (B6) mice, obese db/db and ob/ob mice with leptin dysfunction, and male B6 mice with diet-induced obesity. Mice were injected intraperitoneally with saline (control) and five doses of buprenorphine (0.1, 0.3, 1.0, 3.0, 10 mg/kg). Buprenorphine caused dose-dependent decreases in respiratory frequency while increasing tidal volume, minute ventilation, and respiratory duty cycle. The effects of buprenorphine varied significantly with leptin status and sex. Buprenorphine decreased minute ventilation variability in all mice. The present findings highlight leptin status as an important modulator of respiration and encourage future studies aiming to elucidate the mechanisms through which leptin status alters breathing.