Journal Article

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

Kupferschmidt, David A, Atwood, Brady K, Lovinger, David M

2014

Overview

In this study, the authors show that there are multiple forms of opioid-induced long-term depression (OP-LTD) in the dorsal striatum, each mediated by the mu, delta or kappa opioid receptor. The mu and delta OP-LTD are presynaptic and can summate, but only mu OP-LTD occludes endocannabinoid-induced LTD. Furthermore, mu OP-LTP, but not kappa or delta OP-LTP, is blocked by the analgesic oxycodone. 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.

• Publisher: Springer US,Nature Publishing Group
• Subject: 13/44 / 631/378/2591/2593 / 9/30 / 9/74 / Analgesics / Analgesics, Opioid - administration & dosage / Animal Genetics and Genomics / Animals / Behavioral Sciences / Biological Techniques / Biomedicine / Corpus striatum / Corpus Striatum - drug effects / Corpus Striatum - metabolism / Depression, Mental / Drug abuse / Endocannabinoids - metabolism / Female / Health aspects / Long-Term Synaptic Depression - drug effects / Long-Term Synaptic Depression - physiology / Male / Mice / Mice, Inbred C57BL / Narcotics / Neurobiology / Neuronal Plasticity - drug effects / Neurosciences / Opioid Peptides - metabolism / Opioids / Oxycodone - administration & dosage / Peptides / Physiological aspects / Rats / Rats, Sprague-Dawley / Receptors, Opioid - drug effects / Receptors, Opioid - metabolism / Receptors, Opioid - physiology / Receptors, Opioid, delta - drug effects / Receptors, Opioid, delta - metabolism / Receptors, Opioid, delta - physiology / Receptors, Opioid, kappa - drug effects / Receptors, Opioid, kappa - metabolism / Receptors, Opioid, kappa - physiology / Receptors, Opioid, mu - drug effects / Receptors, Opioid, mu - metabolism / Receptors, Opioid, mu - physiology / Risk factors