Adaptive Changes in α‐2 Adrenoceptor Mediated Responses: Analgesia, Hypothermia and Hypoactivity

Minor, Bruce G.; Danysz, Wojciech; Jonsson, Gösta; Mohammed, Abdul K.; Post, Claes; Archer, Trevor

doi:10.1111/j.1600-0773.1989.tb01145.x

Cited by 15 publications

(9 citation statements)

References 32 publications

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“…Clonidine-induced hypothermia in rats was blocked by the ␣ 2 -adrenergic receptor antagonist yohimbine, and the imidazoline/ ␣ 2 -adrenergic receptor antagonist idazoxan. These findings demonstrate that clonidine-induced hypothermia is mediated by imidazoline/ ␣ 2 -adrenergic receptors and are consistent with previous reports in literature [36,56] . Idazoxan produced a more pronounced blockade of clonidine hypothermia compared to yohimbine, suggesting that imidazoline receptors play an important role in clonidine-induced hypothermia in rats.…”

Section: Discussionsupporting

confidence: 82%

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

Bhalla¹,

Andurkar²,

Gulati³

2011

Pharmacology

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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.

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Section: Discussionsupporting

confidence: 82%

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

Bhalla¹,

Andurkar²,

Gulati³

2011

Pharmacology

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“…In spite of the fact that guanfacine has anxiolytic and sedative effects, whereas caffeine has an anxiogenic effect, the distribution of c-Fos-ir neurons evoked by both compounds was similar in brain areas such as the lateral septum, the PVN, the PVT, and the LPBN (Birnbaum et al 2000;Minor et al 1989). Interpreting our data in terms of guanfacine as a sedative and anxiolytic drug agrees with previous findings that the anxiolytic benzodiazepine lorazepam facilitates GABAergic neurotransmission and also induces c-Fos expression in the CeA (Cohen et al 2003).…”

Section: Discussionmentioning

confidence: 82%

Regulation of Neuronal Activation by Alpha2A Adrenergic Receptor Agonist

Savchenko

Boughter

2010

Neurotox Res

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Stress factors induce neuronal activation in brain areas that are related to anxiety and fear. High doses of caffeine induce neuronal activation with Ca2+ influx followed by expression of the immediate early gene c-fos. In the present study, we investigated c-Fos protein expression in stress-responsive brain areas induced by caffeine, as well as the role of alpha2A receptor in the regulation of neuronal activation. Immunohistochemical analysis showed that an acute effect of caffeine induced c-Fos protein expression in the hippocampus, the bed nucleus of stria terminalis (BNST), the lateral septum, the basolateral and central amygdala, the paraventricular hypothalamic nucleus (PVN), the locus coeruleus, and the lateral parabrachial nucleus (LPBN). However, c-Fos expression was attenuated after repeated treatment of caffeine, spaced 24 h apart, compared to a single acute effect. Alpha2A receptor activation with the agonist guanfacine attenuated the acute effect of caffeine in terms of c-Fos expression in neurons in the CA1-CA3 areas of hippocampus, the locus coeruleus and the LPBN as compared with effect of caffeine alone, whereas the number of c-Fos expressing neurons increased in the lateral septum, the dorsal BNST, the central amygdala, and the PVN, areas that are densely innervated by noradrenergic neurons. Guanfacine alone induced c-Fos protein expression in neurons in the central amygdala, the dorsal BNST, the PVN, the LPBN, and the caudal nucleus of the solitary tract. Guanfacine alone also induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in neurons expressing c-Fos in the dorsal BNST, the central amygdala, and the LPBN. These results suggest that alpha2A receptor activation modulates synaptic transmission in neuronal circuits that are correlated with stress in vivo.

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“…hypoactivity, antinociception, aggressive behaviour) of clonidine, or other a2-adrenoceptor agonists, are quite well documented. Minor et al (1989) indicated that clonidine and guanfacine produced decreases in motor activity that were antagonised by the a2-adrenoceptor antagonist, idazoxan, but unaffected by prior DSP4 treatment while the antinociceptive and hypothermic actions of clonidine and guanfacine were antagonised by idazoxan but potentiated by DSP4 pretreatment. Note that the temporal parameters of activity testing in that study differed from the present one.…”

Section: Discussionmentioning

confidence: 93%

Effects of clonidine and α-adrenoceptor antagonists on motor activity in DSP4-treated mice I: Dose-, time- and parameter-dependency

Archer

Fredriksson

1999

neurotox res

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In three experiments the acute effects of clonidine administration upon locomotor and rearing behaviour of mice pretreated with the selective noradrenaline (NA) neurotoxin, DSP4 (1 x 75 mg/kg, i.p.) 10-12 days previously, were studied. Clonidine (0.01, 0.05, 0.25, 1.25 and 3.0 mg/kg, i.p.) induced a dose-dependent reduction of motor activity during the initial 30min of testing in both DSP4-treated and control mice; this effect was attenuated by DSP4 treatment in the 0.01, 0.05, 0.25 and 3.0 mg/kg dose groups. By the third 30-min period of testing (60-90 min), each clonidine dose group, except the highest (3.0 mg/kg) dose for locomotion and the two highest (1.25 and 3.0 rag/ kg) doses for rearing, induced increases in motor activity in the control mice. In DSP4-treated mice, a large increase in locomotor counts was produced by the 0.05 mg/kg dose of clonidine with lesser increases induced by the 0.01mg/kg dose group, whereas a lesser effect of the 0.05 mg/kg group (30-60 min) was obtained for rearing but a larger effect of the 0.25 mg/ kg group (60-90min). Yohimbine (0.5mg/kg, i.p., 15 min before clonidine) attenuated the suppressive effects of clonidine (0.01 and 0.05 mg/kg) during the initial 30min of testing and markedly increased locomotor and rearing counts, both by itself and in combination with each dose of clonidine, in both DSP4-treated and control mice over the following 90 min of testing. Yohimbine treatment attenuated the large increase in locomotor counts induced by the 0.05 mg/kg dose of clonidine in the NA-denervated mice. Dihydroergotamine (0.5 mg/kg, i.p., 15 min before clonidine) did not antagonise either the initial suppressive effect or the later supersensitivity effect of the 0.05mg/kg dose of clonidine. DSP4 treatment by itself reduced motor activity. The effects of clonidine, dose-and time-dependently, by itself or in coadministration with ~e-adrenoceptor antagonists, in DSP4-treated or control mice displayed denervationinduced supersensitivity that appear to reflect mainly postsynaptic ~2-adrenoceptor mediation.

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Adaptive Changes in α‐2 Adrenoceptor Mediated Responses: Analgesia, Hypothermia and Hypoactivity

Cited by 15 publications

References 32 publications

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

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

Regulation of Neuronal Activation by Alpha2A Adrenergic Receptor Agonist

Effects of clonidine and α-adrenoceptor antagonists on motor activity in DSP4-treated mice I: Dose-, time- and parameter-dependency

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