GENESIS OF BIPHASIC THERMAL RESPONSE TO INTRAPREOPTICALLY MICROINJECTED CLONIDINE

Intrapreoptic (IPO) microinjections of various agents cause unavoidabl e brain tissue injury, often resulting in prostaglandin (PG)-mediated core temperature (T(c)) rises. However, IPO microinjection of the alph a2-adrenoreceptor agonist clonidine (Clo) generally evokes a T(c) 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 do ses of Clo dissolved in pyrogen-free saline (PFS, 1 mul/side). Clo cau sed biphasic hypo-/hyperthermic responses. The initial hypothermia was dose dependent: no decrease in T(c) for 0.1 mug of Clo, -0.4 +/- 0.1- degrees-C for 0.5 mug, -0.9 +/- 0.1-degrees-C for 1.5 mug, and -1.2 +/ - 0.1-degrees-C for 5.0 mug. During the hyperthermic phase, T(c) incre ased to a dose-independent level (1.0-1.5-degrees-C), remaining there up to 5 h postinjection. PFS microinjected IPO also induced hypertherm ia, but without any initial T(c) decrease. This T(c) rise was delayed by 100 min when the cyclooxygenase inhibitor indomethacin (Indo, 50 mu g/mul) was injected. Nontreated animals (time controls) maintained T(c ) at baseline levels during the whole experiment. The alpha2-antagonis t rauwolscine (2 mug/side), microinjected IPO 10 min before Clo(0.5 mu g/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 mug), significantly attenuated the hyperthermic phase. These results confirm that an artifactitious, PG- mediated T(c) rise consequent to nonspecific brain tissue injury conta minates the thermal response to agents (hyper- or hypothermizing) micr oinjected IPO. The similarity of the thermal responses to Clo to those to norepinephrine provides additional evidence that the authentic (hy pothermic) effect of IPO norepinephrine in guinea pigs is mediated via alpha2-adrenergic receptors.