Spinal delta 2-, but not delta 1-, mu-, or kappa-opioid receptors are involved in the tail-flick inhibition induced by beta-endorphin from nucleus raphe obscurus in the pentobarbital-anesthetized rat.

The antinociception induced by beta-endorphin given supraspinally has been previously demonstrated to be mediated by the release of [Met5]enkephalin acting on delta-opioid receptors in the spinal cord. The present study was designed to determine what type of opioid receptors in the spinal cord is involved in beta-endorphin-induced antinociception in the rat. Antinociception was induced by beta-endorphin (0.6 nmol) given into nucleus raphe obscurus and was assessed by the tail-flick test in pentobarbital-anesthesized rats. Naltriben (0.6-6.0 nmol), a selective delta 2-opioid receptor antagonist, given intrathecally dose-dependently attenuated beta-endorphin-induced inhibition of the tail-flick response. On the other hand, 7-benzylidene naltrexone (2.1-64.3 nmol), CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, 0.09-2.8 nmol), or nor-binaltorphimine (1.4-40.8 nmol), selective delta 1-, mu-, and kappa-opioid receptor antagonists, respectively, did not block beta-endorphin-induced antinociception. The results of present study in rats are consistent with previous experiments in mice indicating that spinal delta 2-, but not delta 1-, mu- or kappa-opioid receptors are involved in beta-endorphin-induced inhibition of the tail-flick response.

The clastogenicity of morphine sulfate in vivo.

An opioid analgesic, morphine, and an opioid peptide, beta-endorphin, have been shown to induce chromosome damage, as indicated by an increased frequency of micronucleated lymphocytes, following acute administration to mice. The genotoxic response is opioid receptor-mediated and is abolished in adrenalectomized animals. Further, plasma from morphine-treated animals also induces micronuclei formation in naive lymphocytes in vitro; this response is blocked by inclusion the steroid antagonist RU 486 in the incubation mixture. In addition to the steroid-mediated production of chromosome damage, morphine acts directly on lymphocytes to enhance the clastogenicity of acutely administered cyclophosphamide in manner consistent with depressed DNA repair capacity.

Histologic examination of the rat central nervous system after intrathecal administration of human beta-endorphin.

The objective of this study was to evaluate histologically the toxicity of human beta-endorphin on the rat central nervous system after intrathecal administration. Animals received a single injection of 5 micrograms (n = 9) or 50 micrograms (n = 10) on each of four consecutive days, while others received 50 micrograms (n = 8) as a single dose. The control groups received either physiologic saline (n = 10) during each of four consecutive days or had sham operations (n = 4). Tests for nociception (tail-flick latency), motor function, and reflexes (righting reflex, eye-blink reflex, and inclined plane) were performed 5, 15, 30, 60, and 120 min after injection. Both dosages produced a dose-dependent impact on these parameters. In the 50-micrograms group, there were no significant differences in analgesia between the first and the fourth doses injected. The 50-micrograms dose produced catalepsy in some animals. All changes returned to baseline within 24 h. One animal in the 50-micrograms group developed hind limb paralysis after a single injection. Histologic sections from brain, brain stem, and spinal cord were prepared. No changes in histology were found except for that in the paretic animal, which had anoxic changes in the hippocampus and other cortical areas. Human beta-endorphin produced no neurotoxicity. The effect on nociception, reflexes, and motor function confirmed the results of previous studies.