The thermogenic actions of α₂‐adrenoceptor agonists in reserpinized mice are mediated via a central postsynaptic α₂‐adrenoceptor mechanism

Abstract

1 The dose-related effects of the selective a2-adrenoceptor agonists clonidine, UK-14,304 and B-HT 933 on the body temperature of untreated and reserpine-treated mice were investigated. 2 In untreated mice all three agonists induced a dose-related hypothermia. The highest doses of UK-14,304 and B-HT 933, 3 and lOOmgkg-I respectively, elicited a marked (10C) hypothermia, whereas the maximal hypothermic effect of clonidine (5.50C) was less pronounced and reached a plateau at a dose of 0.5 mg kg-i.p. 3 Reserpine (2.5mg kg-1, s.c.) induced a marked hypothermia in the mouse; 18 h after injection body temperature had decreased to only slightly (0.5-1.50C) above ambient (19'C). 4 All three a2-agonists produced a partial dose-related reversal of reserpine-induced hypothermia; maximal thermogenic responses (9-100C increases in body temperature) were elicited by doses of 0.2, 0.5 and 16mgkg-I i.p. of clonidine, UK-14,304 and B-HT 933 respectively, and the log doseresponse curves for all 3 agonists were bell-shaped. 5 Following intracerebroventricular administration to reserpine-treated mice, the thermogenic response to clonidine was more rapid in onset, and the agonist was 20 fold more potent than when injected i.p.6 The selective a2-adrenoceptor antagonists, idazoxan (0.05-0.5 mgkg-'), Wy 26392 (0.3-5.0mg kg 1) and yohimbine (0.1-1.6mg kg 1) given orally attenuated the thermogenic responses to all 3 agonists in reserpinized mice in a dose-related manner. Pretreatment with a single dose of idazoxan (0.3 mg kg 1, orally) elicited a 6 fold parallel shift to the right in the dose-response curve to clonidine. 7 The selective al-adrenoceptor antagonists, prazosin (lOmgkg 1) and indoramin (3-lOmgkg-'), and the f,-adrenoceptor antagonist, propranolol (lOmgkg 1), only partially attenuated the thermogenic responses to the a2-agonists in reserpinized mice. These effects were variable and not clearly dose-related. 8 Pretreatment of reserpinized mice with the catecholamine synthesis inhibitor, a-methyl-p-tyrosine, markedly attenuated (60-95%) the thermogenic response to the noradrenaline uptake inhibitor, desipramine (0.13-12.5mgkg-1, i.p.), but only slightly reduced (10-35%) that to clonidine (0.032-0.5 mg kg-1, i.p.). 9 These results suggest that a2-adrenoceptor agonists reverse reserpine-induced hypothermia via a central mechanism involving activation of postsynaptic a2-adrenoceptors.

Antidepressant and anxiolytic effects of Garcinia indica fruit rind via monoaminergic pathway

“…The hypothermia is taken as the parameter of depressed behavior, while the rising of body temperature up to normal levels points towards a non-depressed state of mind (Bill et al 1989). Fruit rind/standard drug was administered for 8 days.…”

Altered thermoregulatory responses to clonidine in streptozotocin‐diabetic rats

“…was antagonized by central or periphal yohimbine (Zacny, 1982). The selective a2-agonists, UK-14,304 and BHT 933, also elicit hypothermia by central actions (Colpaert, 1986;Bill et al, 1989). In the present studies, the hypothermia induced in control rats by clonidine was inhibited by the centrally-acting blockers yohimbine or Table 4 Influence of insulin replacement (3-6 i.v.…”

“…In non-diabetic guinea-pigs damage to the pre-optic area leads to hyperthermia and clonidine microinjection leads to a biphasic temperature response, the hyperthermia being dose-dependent (Romanovsky et al, 1993). Animals depeted of central noradrenaline by reserpine treatment also show a thermogenic response to clonidine, by an apparently postsynaptic x2-mechanism (Bill et al, 1989). Thus STZ-treated rats may be considered to manifest a milder form of the hypothalamic noradrenergic deficit and basal hypothermia seen in reserpinised animals.…”

The effects of acute and chronic desipramine on the thermogenic and hypoactivity responses to α2‐agonists in reserpinized and normal mice

“…The thermogenic actions of a2-adrenoceptor agonists in reserpinized mice appear to be mediated primarily via activation of central postsynaptic a2-adrenoceptors (Bill & Stephens, 1984;Bill et al, 1989). In the following study this response to a2-agonists has been used to try to gain further insight into the effects of chronic administration of a NA uptake inhibitor on the sensitivity of central postsynaptic a2-adrenoceptors.…”