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Atg5- and Atg7-dependent autophagy in dopaminergic neurons regulates cellular and behavioral responses to morphine
2017-09-25 | Author: | From:
Atg5- and Atg7-dependent autophagy in dopaminergic neurons regulates cellular and behavioral responses to
morphine. Autophagy, 2017,13(9):1496-1511
Title: Atg5- and Atg7-dependent autophagy in dopaminergic neurons regulates cellular and behavioral responses to morphine.

Author: Su LY, Luo R, Liu Q, Su JR, Yang LX, Ding YQ, Xu L, Yao YG

Publication Name: Autophagy

Pub Year: 2017

Volume: 13

Issue: 9

Page Number: 1496-1511

IF: 8.593

Abstract:

The molecular basis of chronic morphine exposure remains unknown. In this study, we hypothesized that macroautophagy/autophagyof dopaminergic neurons would mediate the alterations of neuronal dendritic morphology and behavioral responses induced bymorphine. Chronic morphine exposure caused Atg5 (autophagy related 5)- and Atg7 (autophagy related 7)-dependent anddopaminergic neuron-specific autophagy resulting in decreased neuron dendritic spines and the onset of addictive behaviors. In cultured primary midbrain neurons, morphine treatment significantly reduced total dendritic length and complexity, and this effect could be reversed by knockdown of Atg5 or Atg7. Mice deficient for Atg5 or Atg7 specifically in the dopaminergic neurons were less sensitive to developing a morphine reward response, behavioral sensitization, analgesic tolerance and physical dependence compared to wild-type mice. Taken together, our findings suggested that the Atg5- and Atg7-dependent autophagy of dopaminergic neuronscontributed to cellular and behavioral responses to morphine and may have implications for the future treatment of drug addiction.

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