Opioid addiction and withdrawal differentially drive long-term depression of inhibitory synaptic transmission in the hippocampus.
Addictive behavior is increasingly accepted as a drug-associated pathological memory in which the hippocampus is profoundly engaged. It has been well documented that adaptations of synaptic plasticity of excitatory transmission in the hippocampus may contribute to opioid addiction. However, it remains unknown whether and how adaptive changes of synaptic plasticity of inhibitory transmission in the hippocampus occurs during opioid abuse. Here, we reported that a single in vivo morphine exposure (SM) did not affect inhibitory long-term depression (I-LTD) in the hippocampus, compared with saline control; while repeated morphine exposure (RM) abolished this I-LTD. Interestingly, opioid withdrawal for 3-5 days after repeated (RMW), but not a single morphine exposure (SMW), largely enhanced I-LTD. More importantly, the I-LTD in single morphine treatment is dependent on presynaptic mechanism since it can be blocked by AM251, a selective cannabinoid receptor 1 antagonist. While the large I-LTD in RMW group is dependent on combinatorial presynaptic and postsynaptic mechanisms since it can be blocked by co-application of AM251 and L-type calcium channel blocker LaCl3. Thus, these results demonstrate that opioid use and withdrawal drive the dynamics of presynaptic and postsynaptic I-LTD expression in the hippocampus that may contribute to the persistent behavioral changes during opioid abuse.
1] Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China [2] Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China [3] Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Huili
H
Han
Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
Zhifang
Z
Dong
1] Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China [2] Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
Yunfang
Y
Jia
Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Rongrong
R
Mao
Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Qixin
Q
Zhou
Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Yuexiong
Y
Yang
Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Liping
L
Wang
Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Lin
L
Xu
Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Jun
J
Cao
D000818:Animals; D002908:Chronic Disease; D006624:Hippocampus / Q000503:physiopathology*; D036881:Long-Term Synaptic Depression; D008297:Male; D009021:Morphine Dependence / Q000503:physiopathology*; D009433:Neural Inhibition; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D009435:Synaptic Transmission