Abstract
Opioids administered by i.c.v. injection produce body temperature (Tb) changes and analgesic responses in rats. The present study was undertaken to investigate the effects on Tb 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, themu receptor agonist Tyr-Pro-N-MePhe-D-Pro-NH2induced 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 A1–17, 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 A1–17microdialyzed into the PAG produced significant changes in Tb. 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 Tb, but not in analgesic, responses to opioids, whereas the PAG is a sensitive area for analgesic, but not for Tb, responses to opioids.
Footnotes
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Send reprint requests to: Dr. Li Xin, Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140.
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↵1 This work was supported by grant DA 00376 from NIDA. Preliminary reports of these results were presented at the 22nd Annual Meeting of the Society for Neuroscience (Anaheim, California, October 1992), the International Symposium on Microdialysis and Allied Analytical Techniques (Indianapolis, Indiana, May 1993) and the 54th Annual Scientific Meeting of the College on Problems of Drug Dependence (Toronto, Canada, June 1993).
- Abbreviations:
- aCSF
- artificial cerebrospinal fluid
- CTAP
- cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2
- Dyn
- dynorphin A1–17
- MPA
- maximum possible analgesia
- nor-BNI
- nor-binaltorphimine
- PAG
- periaqueductal gray
- PL017
- Tyr-Pro-N-MePhe-D-Pro-NH2
- POAH
- preoptic anterior hypothalamus
- Tb
- body temperature
- Received September 19, 1995.
- Accepted December 5, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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