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Vol. 281, Issue 1, 499-507, 1997
Department of Pharmacology, Temple University School of Medicine,
Philadelphia, Pennsylvania
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, 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 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 A1-17
microdialyzed 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.
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