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.
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
Substances
-
Analgesics, Opioid
-
Endocannabinoids
-
Opioid Peptides
-
Receptors, Opioid
-
Receptors, Opioid, delta
-
Receptors, Opioid, kappa
-
Receptors, Opioid, mu
-
Oxycodone