BODY-TEMPERATURE AND ANALGESIC EFFECTS OF SELECTIVE MU-OPIOID AND KAPPA-OPIOID RECEPTOR AGONISTS MICRODIALYZED INTO RAT-BRAIN

Opioids administered by i.c.v. injection produce body temperature (T-b ) changes and analgesic responses in rats. The present study was under taken to investigate the effects on T-b, and analgesia of highly selec tive mu and kappa opioid receptor agonists and antagonists delivered d irectly into the preoptic anterior hypothalamus (POAH) and periaqueduc tal gray (PAG) by the intracerebral microdialysis method. Microdialyze d into the POAH, the mu receptor agonist Tyr-Pro-N-MePhe-D-Pro-NH2 ind uced dose-related hyperthermia that could be prevented or antagonized by the mu receptor antagonist cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-T hr-NH2 or by naloxone, but not by the kappa receptor antagonist nor-bi naltorphimine. The kappa receptor agonist dynorphin A(1-17), microdial yzed into the POAH, induced dose-related hypothermia that was prevente d or antagonized by nor-binaltorphimine but not cyclic D-Phe-Cys-Tyr-D -Trp-Arg-Thr-Pen-Thr-NH2. Neither Tyr-ProN-MePhe-D-Pro-NH2 nor dynorph in A(1-17) microdialyzed into the PAG produced significant changes in T-b. However, these agonists microdialyzed into the PAG produced analg esic 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 i s mediated by the kappa receptor in rats. The POAH is a primary functi onal 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.