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Nat Neurosci. 2014 Apr;17(4):540-8. doi: 10.1038/nn.3652. Epub 2014 Feb 23.

Opioids induce dissociable forms of long-term depression of excitatory inputs to the dorsal striatum.

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Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, Maryland, USA.


As prescription opioid analgesic abuse rates rise, so does the need to understand the long-term effects of opioid exposure on brain function. The dorsal striatum is an important site for drug-induced neuronal plasticity. We found that exogenously applied and endogenously released opioids induced long-term depression (OP-LTD) of excitatory inputs to the dorsal striatum in mice and rats. Mu and delta OP-LTD, although both being presynaptically expressed, were dissociable in that they summated, differentially occluded endocannabinoid-LTD and inhibited different striatal inputs. Kappa OP-LTD showed a unique subregional expression in striatum. A single in vivo exposure to the opioid analgesic oxycodone disrupted mu OP-LTD and endocannabinoid-LTD, but not delta or kappa OP-LTD. These data reveal previously unknown opioid-mediated forms of long-term striatal plasticity that are differentially affected by opioid analgesic exposure and are likely important mediators of striatum-dependent learning and behavior.

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