Mu‐Opioid Receptors (MORs) in Pre‐Botzinger Complex (PBC) Are Involved in Fentanyl Switching of Pulmonary C‐Fibers (PCFs)‐Mediated Rapid Shallow Breathing (RSB) into An Apnea in Anesthetized Rats

Abstract

Our previous study showed that fentanyl (iv), a selective MOR agonist, could switch the PCFs‐mediated RSB into an apnea and that peripheral MORs are necessary for triggering this switch. Here we further tested if central MORs, especially those in the medial nucleus tractus solitarius (mNTS) receiving PCFs’ inputs and the PBC responsible for respiratory rhythmogenesis, were also involved in such switching. Right atrial injection of phenylbiguanide (3–5 μg/kg) was performed to stimulate PCFs in anesthetized rats before and after fentanyl (8 μg/kg, iv) without or with prior central administration of naloxone methiodide (M‐NLX, an opioid receptor antagonist). The central administration was achieved by injecting M‐NLX into the cisterna magna (8 μg/4μl), the mNTS or the PBC (10 mM, 15 nl in each side). Our results showed that phenylbiguanide alone shortened expiratory duration (TE) by 32 ± 6 % (RSB), while it markedly prolonged TE by 5.5‐fold (an apnea) after fentanyl. M‐NLX injected into the cisterna magna or the PBC, but not the mNTS, prevented the fentanyl switching with the TE of RSB slightly but significantly prolonged. This study, along with our previous results, suggests that although peripheral MORs are critical to trigger the fentanyl switching of PCF‐mediated RSB into an apnea, central MORs, especially those in the PBC, are necessary to establish this switching (Supported by ALA RG‐191095‐N and HL 107462).