Aa. Romanovsky et al., GENESIS OF BIPHASIC THERMAL RESPONSE TO INTRAPREOPTICALLY MICROINJECTED CLONIDINE, Brain research bulletin, 31(5), 1993, pp. 509-513
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.