Plethysmography for the assessment of opioid-induced respiratory depression

Opioid-related addiction, overdose and death is a widespread public health crisis. A recent paper published in The Journal of Pharmacology and Experimental Therapeutics by Dr. Renata Marchette working within the National Institute on Drug Abuse Intramural Research Program provides a model example of the how plethysmography can be used to assess ventilatory behavior changes that occur with opioid administration.

Using emka & SCIREQ plethysmography chambers and IOX software, the authors developed a rat model of acute and chronic fentanyl and heroin I.V. administration. Surgical catheter implantation and the use of Instech swivels, integrated with the plethysmography chambers, allowed for ventilatory parameters to be recorded, without removing subjects from the chambers for drug administration. The paper presents minute ventilation, tidal volume, inspiratory time, peak inspiratory flow, and apneic pause (expiratory time/relaxation time) – 1] data from a series of experiments that examine dose-responses, intermittent acute administration, and chronic administration, in both male and female subjects.

Respiratory depression is a well-known consequence of both heroin and fentanyl, which the dose-response experiments capture, demonstrating a more sustained effect with heroin over fentanyl (see figure 1).

Figure 1: Minute ventilation following a single I.V. dose of herioin or fentanyl.

No tolerance was observed with intermittent acute administration; however chronic administration of fentanyl produced a subsequently shortened respiratory depression to both heroin and fentanyl (a tolerance/ cross-tolerance effect), an effect which persisted in males only during withdrawal (see figure 2).

Figure 2: Minute volume in male and female rats during withdrawal from chronic fentanyl exposure, with an acute administration of heroin or fentanyl.

This study provides both an extremely well-constructed study design for the assessment opioid-induced respiratory depression and a compelling, in-depth analysis of plethysmography data. Models and experimental data, such as those presented in this paper will be critical to developing the tools required to address the on-going opioid epidemic.


Heroin- and Fentanyl-Induced Respiratory Depression in a Rat Plethysmography Model: Potency, Tolerance, and Sex Differences. (2023). Marchette, R., et al. Journal of Pharmacology and Experimental Therapeutics, 385: 117-134.

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