Regulation of morphine-induced synaptic alterations: Role of oxidative stress, ER stress, and autophagy

Yu Cai, Lu Yang, Guoku Hu, Xufeng Chen, Fang Niu, Li Yuan, Han Liu, Huangui Xiong, Jyothi Arikkath, Shilpa J Buch

Research output: Contribution to journalArticle

27 Scopus citations


Our findings suggest that morphine dysregulates synaptic balance in the hippocampus, a key center for learning and memory, via a novel signaling pathway involving reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and autophagy. We demonstrate in this study that exposure of morphine to hippocampal neurons leads to a reduction in excitatory synapse densities with a concomitant enhancement of inhibitory synapse densities via activation of the μ opioid receptor. Furthermore, these effects of morphine are mediated by up-regulation of intracellular ROS from NAD PH oxidase, leading, in turn, to sequential induction of ER stress and autophagy. The detrimental effects of morphine on synaptic densities were shown to be reversed by platelet-derived growth factor (PDGF), a pleiotropic growth factor that has been implicated in neuroprotection. These results identify a novel cellular mechanism involved in morphine- mediated synaptic alterations with implications for therapeutic interventions by PDGF.

Original languageEnglish (US)
Pages (from-to)245-258
Number of pages14
JournalJournal of Cell Biology
Issue number2
StatePublished - Jan 1 2016


ASJC Scopus subject areas

  • Cell Biology

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