PMID- 32553889 OWN - NLM STAT- MEDLINE DCOM- 20211005 LR - 20211005 IS - 1878-1519 (Electronic) IS - 1569-9048 (Linking) VI - 280 DP - 2020 Sep TI - Activation of mu-opioid receptors differentially affects the preBotzinger Complex and neighbouring regions of the respiratory network in the adult rabbit. PG - 103482 LID - S1569-9048(20)30140-3 [pii] LID - 10.1016/j.resp.2020.103482 [doi] AB - The role of the different components of the respiratory network in the mediation of opioid-induced respiratory depression is still unclear. We investigated the contribution of the preBotzinger Complex (preBotC) and the neighbouring Botzinger Complex (BotC) and inspiratory portion of the ventral respiratory group (iVRG) in anesthetized, vagotomized, paralyzed and artificially ventilated adult rabbits making use of bilateral microinjections (30-50 nl) of the mu-opioid receptor agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO). Dose-dependent effects were observed. In the preBotC and the BotC 0.1 mM DAMGO microinjections caused mainly reductions in peak phrenic amplitude associated with tonic phrenic activity and irregular (ataxic) patterns of breathing that were more pronounced in the preBotC. Apneic effects developed at 0.5 mM. In the iVRG DAMGO provoked decreases in amplitude and frequency of phrenic bursts at 0.1 mM and apnea at 0.5 mM. Local 5 mM naloxone reversed the apneic effects. The results imply that different components of the respiratory network may contribute to opioid-induced respiratory disorders. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Cinelli, Elenia AU - Cinelli E AD - Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Universita degli Studi di Firenze, Viale G.B. Morgagni 63, 50134, Firenze, Italy. Electronic address: elenia.cinelli@unifi.it. FAU - Bongianni, Fulvia AU - Bongianni F AD - Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Universita degli Studi di Firenze, Viale G.B. Morgagni 63, 50134, Firenze, Italy. FAU - Pantaleo, Tito AU - Pantaleo T AD - Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Universita degli Studi di Firenze, Viale G.B. Morgagni 63, 50134, Firenze, Italy. FAU - Mutolo, Donatella AU - Mutolo D AD - Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Universita degli Studi di Firenze, Viale G.B. Morgagni 63, 50134, Firenze, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200615 PL - Netherlands TA - Respir Physiol Neurobiol JT - Respiratory physiology & neurobiology JID - 101140022 RN - 0 (Analgesics, Opioid) RN - 0 (Narcotic Antagonists) RN - 0 (Receptors, Opioid, mu) RN - 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-) RN - 36B82AMQ7N (Naloxone) SB - IM MH - Analgesics, Opioid/*pharmacology MH - Animals MH - Apnea/chemically induced/physiopathology MH - Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/*pharmacology MH - Medulla Oblongata/*drug effects/metabolism MH - Microinjections MH - Naloxone/pharmacology MH - Narcotic Antagonists/pharmacology MH - Neurons MH - Phrenic Nerve/*drug effects/physiopathology MH - Rabbits MH - Receptors, Opioid, mu/agonists/*metabolism MH - Respiratory Center/*drug effects/metabolism MH - Respiratory Insufficiency/*chemically induced/physiopathology OTO - NOTNLM OT - Control of breathing OT - Medullary respiratory network OT - Opioid-induced respiratory depression OT - preBotzinger Complex OT - mu-Opioid receptors EDAT- 2020/06/20 06:00 MHDA- 2021/10/06 06:00 CRDT- 2020/06/20 06:00 PHST- 2020/03/16 00:00 [received] PHST- 2020/06/05 00:00 [revised] PHST- 2020/06/12 00:00 [accepted] PHST- 2020/06/20 06:00 [pubmed] PHST- 2021/10/06 06:00 [medline] PHST- 2020/06/20 06:00 [entrez] AID - S1569-9048(20)30140-3 [pii] AID - 10.1016/j.resp.2020.103482 [doi] PST - ppublish SO - Respir Physiol Neurobiol. 2020 Sep;280:103482. doi: 10.1016/j.resp.2020.103482. Epub 2020 Jun 15.