title: Opioids induce dissociable forms of long-term depression of excitatory inputs to the dorsal striatum.
abstract: 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.
authors.affiliation: Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Brady K
authors.initials: BK
authors.lastname: Atwood
authors.affiliation: Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Kupferschmidt
authors.affiliation: Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Lovinger
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism; D005260:Female; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects*; D018847:Opioid Peptides / Q000378:metabolism; D010098:Oxycodone / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D063388:Endocannabinoids; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D010098:Oxycodone