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

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


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Animals
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Endocannabinoids / metabolism
  • Female
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / drug effects*
  • Opioid Peptides / metabolism
  • Oxycodone / administration & dosage
  • 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


  • Analgesics, Opioid
  • Endocannabinoids
  • Opioid Peptides
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Oxycodone