期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 35, 期 3, 页码 456-469出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2007.04.007
关键词
opioid receptor; dentritic spines; receptor internalization; synaptic plasticity; addiction
资金
- NIDA NIH HHS [DA016674, K05-DA70554, K05 DA070554, DA000564, DA007339, R01 DA007339, DA01806, K05 DA000513, R01 DA000564, R01 DA020582-01A1, R01DA020582, K05-DA000513, R01 DA016674, R56 DA000564, P50 DA011806, R01 DA020582] Funding Source: Medline
This study has examined the relationship between the effects of opioids on the internalization of ran opioid receptors (MORs) and the morphology of dendritic spines. Several opioids (morphine, etorphine, DAMGO or methadone) were applied to cultured hippocampal neurons. Live imaging and biochemical techniques were used to examine the dynamic changes in MOR internalization and spine morphology. This study reveals that MOR internalization can regulate opioid-induced morphological changes in dendritic spines: (1) Chronic treatment with morphine, which induced minimal receptor internalization, caused collapse of dendritic spines. In contrast, internalizing opioids such as DAMGO and etorphine induced the emergence of new spines. It reveals that opioid-induced changes in spines vary greatly depending on how the applied opioid agonist affects MOR internalization. (2) The blockade of receptor internalization by dominant negative mutant of dynamin, K44E, reversed the effects of DAMGO and etorphine. It indicates that receptor internalization is necessary for the distinct effects of DAMGO and etorphine on spines. (3) In neurons that were cultured from MOR knock-out mice and had been co-transfected with DsRed and MOR-GFP, morphine caused collapse of spines whereas DAMGO induced emergence of new spines, indicating that opioids can alter the structure of spines via postsynaptic MORs. (4) Methadone at a low concentration induced minimal internalization and had effects that were similar to morphine. At a high concentration, methadone induced robust internalization and had effects that are opposite to morphine. The concentration-dependent opioid-induced changes in dendritic spines might also contribute to the variation in the effects of individual opioids. Published by Elsevier Inc.
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