title: Morphine and DAMGO produce an opposite effect on presynaptic glutamate release via different downstream pathways of μ opioid receptors in the basolateral amygdala.
abstract: Increasing evidence demonstrates that different opioids, while acting μ opioid receptors, can activate distinct downstream responses, a phenomenon termed functional selectivity or biased agonism. The present study designed experiments to test whether the μ receptor agonist morphine and D-Ala(2), N-Me-Phe(4), Gly(5)-ol-enkephalin (DAMGO) had a different effect on presynaptic glutamate release in the basolateral amygdala (BLA) and whether this difference was due to their biased agonism at μ receptors. The results showed that DAMGO markedly decreased the frequency of sEPSCs in pyramidal cells of BLA. The concentration-dependence experiment showed that DAMGO dose-dependently decreased the frequency of sEPSCs. Morphine markedly increased the frequency of sEPSCs in pyramidal cells of BLA. The concentration-dependence experiment showed that morphine dose-dependently increased the frequency of sEPSCs. We also used PPF of EPSC as another indicator of presynaptic glutamate release to confirm the opposite effect of morphine and DAMGO on the glutamate release. Further mechanism studies showed that the opposite effect of morphine and DAMGO on the glutamate release was via the activation of μ receptors, but the downstream signaling pathways of μ receptors were different: DAMGO inhibited the glutamate release via μ receptor-Gi protein- PLA2-AA signaling pathway, whereas morphine promoted the glutamate release via μ receptor-Gi protein-PKC-ERK1/2-synapsin I signaling pathway.
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Hualan
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Du
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Song
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China. Electronic address: pzheng@shmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D009294:Narcotics; D018377:Neurotransmitter Agents; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018698:Glutamic Acid; D009020:Morphine
keywords: ERK1/2; Enkephalin; Glutamate release; Morphine; PLA(2); μ receptors