Supersensitivity of spinal opioid receptors to antagonists in intrathecal butorphanol and morphine dependence.
The purpose of this investigation was to evaluate changes in the sensitivity of spinal opioid receptors to selective antagonists in rats rendered dependent on intrathecal (i.t.) butorphanol and morphine. Using quantitative autoradiography, competitive binding assays with selective opioid antagonists were performed in the spinal cord sections of i.t. butorphanol- and morphine-dependent rats in which withdrawal was precipitated by i.t. naloxone. In butorphanol-dependent rats, the spinal kappa-opioid receptor developed a greater degree of antagonist supersensitivity than the spinal delta- and mu-opioid receptors did. In contrast, the spinal mu-opioid receptor became more sensitive than the delta-opioid receptor in morphine-dependent rats. These results indicate that differential supersensitivity of spinal opioid receptors was induced after chronic i.t. infusions of butorphanol and morphine.
Wongchanapai
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216, USA.
Tsang
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D000818:Animals; D002077:Butorphanol / Q000008:administration & dosage / Q000009:adverse effects*; D007278:Injections, Spinal; D008297:Male; D009021:Morphine Dependence / Q000188:drug therapy*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D019966:Substance-Related Disorders / Q000188:drug therapy*
D009292:Narcotic Antagonists; D002077:Butorphanol