Study of Adrenergic, Imidazoline, and Endothelin Receptors in Clonidine-, Morphine-, and Oxycodone-Induced Changes in Rat Body Temperature

Abstract

Objectives: The potentiation of morphine or oxycodone analgesia by endothelin-A (ET_A) receptor antagonists and imidazoline/α₂-adrenergic agonists is well documented. However, the effect of morphine or oxycodone in combination with an ET_A receptor antagonist or an imidazoline/α₂ adrenergic agonist on body temperature is not known. The present study was carried out to study the role of ET_A and imidazoline/α₂ adrenergic receptors in body temperature effects of morphine, oxycodone, and clonidine in rats. Methods: Body temperature was determined in male Sprague-Dawley rats treated with morphine, oxycodone, or clonidine. Yohimbine, idazoxan, and BMS182874 were used to determine the involvement of α₂-adrenergic, imidazoline, and ET_A receptors, respectively. Key Findings: Morphine and oxycodone produced hyperthermia which was not affected by α₂-adrenergic antagonist yohimbine, imidazoline/α₂-adrenergic antagonist idazoxan, or ET_A receptor antagonist BMS182874. Clonidine alone produced hypothermia that was comparable to the hypothermia observed with clonidine plus morphine or oxycodone. The hypothermic effect of clonidine was blocked by idazoxan and yohimbine. The blockade by idazoxan was more pronounced compared to yohimbine. Clonidine hypothermia was not affected by BMS182874. Conclusions: This is the first report demonstrating that ET_A receptors do not influence morphine- and oxycodone- induced hyperthermia or clonidine-induced hypothermia. Imidazoline receptors and α₂-adrenergic receptors are involved in clonidine-induced hypothermia, but not in morphine- and oxycodone-induced hyperthermia.

Breathing and temperature control disrupted by morphine and stabilized by clonidine in neonatal rats

“…(Bhalla et al 2011). Clonidine is effective in the treatment of post-anesthetic shivering (Joris et al 1993).…”

Assessment of the Analgesic Effect of Centhaquin in Mouse Tail Flick and Hot-Plate Tests

“…Centhaquin is a 4-arylpiperazine derivative that produces centrally mediated hypotension in various animal models in a manner similar to clonidine [4][5][6][7] . In addition to its hypotensive properties, clonidine is known to produce analgesia [10,18,20] and hypothermia [11,13,31,36] . Clonidine also potentiates the analgesic effects of morphine and other opioids [18][19][20][21] .…”

“…The clinical use of clonidine and other ␣ 2 -adrenergic agonists as adjuvant analgesics [22][23][24][25] , in managing opioid tolerance and dependence [26,27] , as well as in managing opioid withdrawal [28][29][30] , is well documented. Clonidineinduced hypothermia is blocked by the ␣ 2 -adrenergic antagonist yohimbine [11,31] as well as by idazoxan, suggesting the involvement of imidazoline/ ␣ 2 -adrenergic receptors in clonidine-induced hypothermia.…”

“…Clonidine also produces analgesia [9,10] and hypothermia [11][12][13] . The analgesic effects of clonidine are proposed to have peripheral [14] and central components [15,16] .…”

Involvement of α2‐adrenoceptors, imidazoline, and endothelin‐A receptors in the effect of agmatine on morphine and oxycodone‐induced hypothermia in mice

“…Treatment with ET A receptor antagonists also restores opioid analgesia in opioid tolerant rats and mice . In addition to their analgesic effects, opioid agonists are known to alter body temperature . Studies have shown that mu receptor selective antagonists, CTAP, and beta‐funaltrexamine block the hyperthermic response induced by mu opioid receptor selective agonists, DAMGO, and PLO17 .…”