title: The endocannabinoid system regulates synaptic transmission in nucleus accumbens by increasing DAGL-α expression following short-term morphine withdrawal.
abstract: OBJECTIVE
  The endocannabinoid (eCB) system is involved in pathways that regulate drug addiction and eCB-mediated synaptic plasticity has been linked with addictive behaviours. Here, we investigated the molecular mechanisms underlying the changes in eCB-dependent synaptic plasticity in the nucleus accumbens core (NAcc) following short-term withdrawal from repeated morphine treatment.
  
  
  METHODS
  Conditioned place preference (CPP) was used to evaluate the rewarding effects of morphine in rats. Evoked inhibitory postsynaptic currents of medium spiny neurons in NAcc were measured using whole-cell patch-clamp recordings. Changes in depolarization-induced suppression of inhibition (DSI) in the NAcc were assessed to determine the effect of short-term morphine withdrawal on the eCB system. To identify the potential modulation mechanism of short-term morphine withdrawal on the eCB system, the expression of diacylglycerol lipase α (DGL-α) and monoacylglycerol lipase was detected by Western blot analysis.
  
  
  RESULTS
  Repeated morphine administration for 7 days induced stable CPP. Compared with the saline group, the level of DSI in the NAcc was significantly increased in rats after short-term morphine withdrawal. Furthermore, this increase in DSI coincided with a significant increase in the expression of DGL-α.
  
  
  CONCLUSIONS
  Short-term morphine withdrawal potentiates eCB modulation of inhibitory synaptic transmission in the NAcc. We also found that DGL-α expression was elevated after short-term morphine withdrawal, suggesting that the eCB 2-arachidonyl-glycerol but not anandamide mediates the increase in DSI. These findings provide useful insights into the mechanisms underlying eCB-mediated plasticity in the NAcc during drug addiction.
  
  
  BACKGROUND
  This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xing-Qin
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wei-Xin
authors.initials: WX
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Heng
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Gao
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology; D063388:Endocannabinoids / Q000378:metabolism*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D009433:Neural Inhibition; D009714:Nucleus Accumbens / Q000378:metabolism / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D009435:Synaptic Transmission
chemical_list: D063388:Endocannabinoids; D009020:Morphine; D008071:Lipoprotein Lipase