Respiratory physiology & neurobiology
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Respir Physiol Neurobiol · Apr 2020
Kölliker-Fuse/Parabrachial complex mu opioid receptors contribute to fentanyl-induced apnea and respiratory rate depression.
Overdoses caused by the opioid agonist fentanyl have increased exponentially in recent years. Identifying mechanisms to counter progression to fatal respiratory apnea during opioid overdose is desirable, but difficult to study in vivo. The pontine Kölliker-Fuse/Parabrachial complex (KF/PB) provides respiratory drive and contains opioid-sensitive neurons. ⋯ Higher concentrations caused prolonged apnea, interrupted by occasional apneustic-like bursts. Application of CTAP, a selective mu opioid receptor antagonist, directly into the KF/PB complex reversed and prevented fentanyl-induced apnea by increasing the frequency of apneustic-like bursting. These results demonstrate that countering opioid effects in the KF/PB complex is sufficient to restore phasic respiratory output at a rate similar to pre-fentanyl conditions, which could be beneficial in opioid overdose.