Supersensitivity of spinal opioid receptors to antagonists in intrathecal butorphanol and morphine dependence

Abstract

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 κ-opioid receptor developed a greater degree of antagonist supersensitivity than the spinal δ- and μ-opioid receptors did. In contrast, the spinal μ-opioid receptor became more sensitive than the δ-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.