Effects of inhaled aerosolized carfentanil on real-time physiological responses in mice: a preliminary evaluation of naloxone

Abstract

This study examined the real-time exposure–response effects of aerosolized carfentanil (CRF) on opioid-induced toxicity, respiratory dynamics and cardiac function in mice. Unrestrained, conscious male CD-1 mice (25–30 g) were exposed to 0.4 or 4.0 mg/m³ of aerosolized CRF for 15 min (Ct = 6 or 60 mg min/m³) in a whole-body plethysmograph chamber. Minute volume (MV), core body temperature (T_c), mean arterial blood pressure (MAP) and heart rate (HR) were evaluated in animals exposed to CRF or sterile H₂O. Loss of consciousness and Straub tail were observed in before 1 min following initiation of exposure to 6 or 60 mg min/m³ of CRF. Clinical signs of opioid-induced toxicity were observed in a dose-dependent manner. Exposure to 6 or 60 mg min/m³ of CRF resulted in significant decrease in MV as compared to the controls. MAP, HR and T_c decreased 24 h in animals exposed to either 6 or 60 mg min/m³ of CRF as compared to the controls. Post-exposure administration of naloxone (NX, 0.05 mg/kg, i.m.) did not increase the MV of animals exposed to CRF to control levels within 24 h, but decreased clinical signs of opioid-induced toxicity and the duration of respiratory depression. This is the first study to evaluate real-time respiratory dynamics and cardiac function during exposure and up to 24 h post-exposure to CRF. The evaluation of toxicological signs and respiratory dynamics following exposure to CRF will be useful in the development of therapeutic strategies to counteract the ongoing threat of abuse and overuse of opioids and their synthetic variants.

Keywords:

• Cardiac function
• carfentanil
• inhalation exposure
• naloxone
• respiratory dynamics
• respiratory toxicology

Acknowledgements

The views expressed herein are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense, or the US Government. This work was supported by the Defense Threat Reduction Agency.

Disclosure statement

The authors have nothing to disclose.

Additional information

Funding

This work was supported by the Defense Threat Reduction Agency.