Increased release of excitatory amino acids in rat locus coeruleus in kappa-opioid agonist dependent rats precipitated by nor-binaltorphimine.
Extracellular fluid levels of glutamate and aspartate in the locus coeruleus (LC) during nor-binaltorphimine (nor-BNI)-precipitated withdrawal from butorphanol, (5alpha,7alpha,8beta)-(+)-N-methyl-N-[7-(1-pyrrolidiny l)-1-oxaspiro [4,5] dec-8-yl]-benzeneacetamide (U-69,593), or morphine were measured in rats. When the microdialysis probe was located in the core of the LC, increases in glutamate and aspartate were noted after nor-BNI (48 nmol/50 microl, LC)-precipitated withdrawal in rats that had been intracerebroventricularly infused with butorphanol (26 nmol/1 microl/h) or U-69,593 (26 nmol/10 microl/h) for 3 days. The glutamate and aspartate levels in the LC markedly increased in the butorphanol- or U-69,593-dependent rats within 60 min following administration of nor-BNI. However, there was no significant increase in levels of glutamate, and only a slight increase in levels of aspartate, after nor-BNI treatment of the morphine (26 nmol/1 microl/h)-infused rats. Behavioral signs of withdrawal (teeth-chattering, wet-dog shakes, etc.) were observed following nor-BNI challenge in the butorphanol- or U-69,593-infused rats, with only minimal signs in the morphine-infused rats, and none in the saline-infused controls. These results directly suggest that kappa-opioid receptors and excitatory amino acids within the LC mediate withdrawal in animals dependent on butorphanol or U-69,593, but not on morphine.
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505, USA.
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D000818:Animals; D044482:Benzeneacetamides; D002077:Butorphanol / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D018846:Excitatory Amino Acids / Q000378:metabolism*; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000009:adverse effects; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000009:adverse effects; D011759:Pyrrolidines / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D019966:Substance-Related Disorders
D044482:Benzeneacetamides; D018846:Excitatory Amino Acids; D009292:Narcotic Antagonists; D009294:Narcotics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D009271:Naltrexone; D009020:Morphine; C045444:U 69593; D002077:Butorphanol