Preoptic norepinephrine-induced hypothermia is mediated by alpha 2-adrenoceptors

Abstract

We have shown previously that norepinephrine (NE) microdialyzed into the preoptic area of conscious guinea pigs evokes a fall in core temperature (Tco) that is mediated by a reduction in metabolic rate. To identify the adrenoceptor subtype(s) involved in this effect, we microdialyzed intrapreoptically various adrenergic agonists or antagonists singly or in combinations. Tco and ear skin temperatures of the animals were monitored throughout the experiments. alpha 1-, beta-, beta 1-, and beta 2-agonists and antagonists did not induce significant Tco changes. Although the alpha 2-antagonists yohimbine (Yoh) and rauwolscine (Rau) did not have thermal effects per se, the alpha 2-agonist clonidine evoked dose-dependent Tco falls that were abolished by codialyzed Yoh and Rau. The microdialysis of NE evoked, as before, a 0.7 +/- 0.2 degrees C Tco fall; it was abolished by the codialyzed alpha-antagonist phentolamine, Yoh, and Rau but not by the beta-antagonist propranolol. No adrenoceptor agonist induced changes in ear skin temperature. These results indicate that the hypothermizing effect of intrapreoptically microdialyzed NE is achieved by a reduction in metabolic heat production, mediated by alpha 2-adrenoceptors.

The effects of Cirazoline, an alpha-1 adrenoreceptor agonist, on the firing rates of thermally classified anterior hypothalamic neurons in rat brain slices

“…Since norepinephrine also acts at alpha-2 ARs to produce an initial hypothermic effect (Quan et al, 1992), it may be presumed that their activation results in responses for these two populations of POAH neurons that contrast those we have shown for the alpha-1 AR agonist Cirazoline, but this remains to be tested. This early hyperthermia likely attenuates due to eventual desensitization at the postsynaptic alpha-1 ARs, the induction of COX-2 expression by activation of alpha-2 ARs, ensuing PGE 2 synthesis, and action at Prostaglandin E receptors (EP; presumably the EP 3 subtype) which contribute the late phase of fever (Feleder et al, 2007;Lazarus et al, 2007;Oka, 2004).…”

The Involvement of Brain Monoamines in the Onset of Hyperthermic Central Fatigue

“…Noradrenaline administered in the preoptic area induces a hypothermic response because of a reduction in the metabolic rate (Quan et al, 1991). This response has been shown to be mediated by -2 receptors, as demonstrated by the fact that an -2 agonist evoked a dose-dependent decrease in body temperature that was abolished by an -2 antagonist (Quan et al, 1992). Similar results were found after noradrenaline activation in the anterior hypothalamus during rest and exercise (Feleder et al, 2004;Gisolfi & Christman, 1980).…”

“…The literature points out that the divergent thermal effects of noradrenaline depend on the t y p e o f r e c e p t o r t h a t i s b e i n g s t imulated. Therefore, it seems that -1 noradrenergic receptors mediate a rise in body temperature, while -2 noradrenergic receptors are involved in a fall in body temperature (Feleder et al, 2004;Imbery et al, 2008;Quan et al, 1991Quan et al, , 1992. Noradrenaline administered in the preoptic area induces a hypothermic response because of a reduction in the metabolic rate (Quan et al, 1991).…”

Altered thermoregulatory responses to clonidine in streptozotocin‐diabetic rats

“…Administration of noradrenaline or clonidine to the preoptic area of the guinea-pig hypothalamus elicits hypothermia that is blocked by coadministration of yohimbine or rauwolscine (Quan et al, 1992). Earlier studies have shown that the hypothermia caused by low dose clonidine (0.05 mg kg-', i.p.)…”

“…The lack of inhibitory effect of naloxone indicated that the hypothermia elicited by clonidine does not depend on opioid-mediated mechanisms. The lack of sensitivity to an a2-induced hypothermia in STZ-treated rats could also be due to abnormality at central or peripheral sites, since the hypothalamic control is exercised through reduction in metabolic heat production (Quan et al, 1992). The similarity of the response to the peripheral vasodilator nicotinic acid would appear to exclude gross vascular changes in diabetes as causes of the inversion of the thermoregulatory response to clonidine.…”