Vol. 281, Issue 1, 499-507, 1997

Body Temperature and Analgesic Effects of Selective Mu and Kappa Opioid Receptor Agonists Microdialyzed into Rat Brain¹

Li Xin, Ellen B. Geller and Martin W. Adler

Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania

Opioids administered by i.c.v. injection produce body temperature (T_b) changes and analgesic responses in rats. The present study was undertaken to investigate the effects on T_b and analgesia of highly selective mu and kappa opioid receptor agonists and antagonists delivered directly into the preoptic anterior hypothalamus (POAH) and periaqueductal gray (PAG) by the intracerebral microdialysis method. Microdialyzed into the POAH, the mu receptor agonist Tyr-Pro-N-MePhe-D-Pro-NH₂ induced dose-related hyperthermia that could be prevented or antagonized by the mu receptor antagonist cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH₂ or by naloxone, but not by the kappa receptor antagonist nor-binaltorphimine. The kappa receptor agonist dynorphin A_1-17, microdialyzed into the POAH, induced dose-related hypothermia that was prevented or antagonized by nor-binaltorphimine but not cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH₂. Neither Tyr-Pro-N-MePhe-D-Pro-NH₂ nor dynorphin A_1-17 microdialyzed into the PAG produced significant changes in T_b. However, these agonists microdialyzed into the PAG produced analgesic responses that did not occur after administration into the POAH. These results support the hypothesis that the hyperthermic response to opioids is mediated by the mu receptor and the hypothermic response is mediated by the kappa receptor in rats. The POAH is a primary functional area in T_b, but not in analgesic, responses to opioids, whereas the PAG is a sensitive area for analgesic, but not for T_b, responses to opioids.