Genesis of biphasic thermal response to intrapreoptically microinjected clonidine.
Intrapreoptic (IPO) microinjections of various agents cause unavoidable brain tissue injury, often resulting in prostaglandin (PG)-mediated core temperature (Tc) rises. However, IPO microinjection of the alpha 2-adrenoreceptor agonist clonidine (Clo) generally evokes a Tc fall, seemingly avoiding the influence of injury due to the microinjection procedure per se. To clarify this, we microinjected bilaterally into the preoptic/anterior hypothalamus of conscious guinea pigs various doses of Clo dissolved in pyrogen-free saline (PFS, 1 microliter/side). Clo caused biphasic hypo-/hyperthermic responses. The initial hypothermia was dose dependent: no decrease in Tc for 0.1 microgram of Clo, -0.4 +/- 0.1 degree C for 0.5 microgram, -0.9 +/- 0.1 degree C for 1.5 microgram, and -1.2 +/- 0.1 degree C for 5.0 micrograms. During the hyperthermic phase, Tc increased to a dose-independent level (1.0-1.5 degrees C), remaining there up to 5 h postinjection. PFS microinjected IPO also induced hyperthermia, but without any initial Tc decrease. This Tc rise was delayed by 100 min when the cyclooxygenase inhibitor indomethacin (Indo, 50 micrograms/microliters) was injected. Nontreated animals (time controls) maintained Tc at baseline levels during the whole experiment. The alpha 2-antagonist rauwolscine (2 micrograms/side), microinjected IPO 10 min before Clo (0.5 microgram/side), abolished the hypothermic without affecting the hyperthermic response phase; Indo (10 mg/kg), injected intramuscularly 20 min after the IPO microinjection of Clo (0.5 microgram), significantly attenuated the hyperthermic phase. These results confirm that an artifactitious, PG-mediated Tc rise consequent to nonspecific brain tissue injury contaminates the thermal response to agents (hyper- or hypothermizing) microinjected IPO.(ABSTRACT TRUNCATED AT 250 WORDS)
Romanovsky
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AA
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
Shido
O
O
Ungar
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Blatteis
C M
CM
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D011301:Preoptic Area; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013238:Stereotaxic Techniques; D015016:Yohimbine / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D015016:Yohimbine; D011451:Prostaglandin-Endoperoxide Synthases; D003000:Clonidine; D007213:Indomethacin