Precipitated kappa-opioid receptor agonist withdrawal increase glutamate in rat locus coeruleus.
Extracellular fluid levels of excitatory amino acids (glutamate, Glu; and aspartate, Asp) in the locus coeruleus and the behavioral signs during naloxone-precipitated withdrawal from kappa-opioid receptor agonists, butorphanol and (5 alpha, 7 alpha, 8 beta) -(+)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]-be nzaneacetamide (U-69,593), were investigated by in vivo microdialysis. Increases in levels of Glu, but not of Asp, were noted after naloxone (12 or 48 nmol/5 microliters, locus coeruleus)-precipitated withdrawal in the rats which had been intracerebroventricularly infused with butorphanol (26 nmol/1 microliters/h) or U-69,593 (26 nmol/10 microliters/h) for 3 days. The Glu levels in the locus coeruleus increased following administration of naloxone before and during the first 15-min sample after the precipitation of withdrawal in the butorphanol- or U-69,593-dependent rats. Furthermore, behavioral evidence of withdrawal (teeth-chattering, wet-dog shakes, etc.) was detected following the naloxone challenge in the butorphanol- and U-69,593-infused rats, but not in saline-infused controls. These results provide direct evidence to support the role of excitatory amino acids within the locus coeruleus in butorphanol or U-69,593 withdrawal.
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505, USA.
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D000700:Analgesics / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D044482:Benzeneacetamides; D002077:Butorphanol / Q000009:adverse effects; D018698:Glutamic Acid / Q000378:metabolism*; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011759:Pyrrolidines / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013375:Substance Withdrawal Syndrome
D000700:Analgesics; D044482:Benzeneacetamides; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D001224:Aspartic Acid; D009270:Naloxone; D018698:Glutamic Acid; C045444:U 69593; D002077:Butorphanol