Relevance of the use of [<sup>3</sup>H]‐clonidine to identify imidazoline receptors in the rabbit brainstem

Bricca, Giampiero; Zhang, J.; Greney, Hugues; Dontenwill, Monique; Stutzmann, J; Belcourt, A.; Bousquet, Pascal

doi:10.1111/j.1476-5381.1993.tb13998.x

Cited by 38 publications

(18 citation statements)

References 41 publications

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“…UK 14 304, which is a highly selective a 2 -adrenoceptor agonist (Cambridge, 1981) with low affinity for I 1 receptors (I 1 /a 2 affinity ratio ¼ 0.01; Bricca et al, 1993;Ernsberger et al, 1992), was used to support our hypothesis that agmatine enhances the effects of morphine on producing CPP via a mechanism involving a 2 -adrenoceptors. UK 14 304 (0.5 mg/kg) in combination with a subeffective dose of morphine produces significant CPP.…”

Section: Discussionmentioning

confidence: 99%

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Tahsili-Fahadan

Yahyavi-Firouz-Abadi

Khoshnoodi

et al. 2005

Neuropsychopharmacol

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The effects of agmatine, an endogenous polyamine metabolite formed by decarboxylation of L-arginine, and its combination with morphine on conditioned place preference (CPP) has been investigated in male mice. Our data show that subcutaneous administration of morphine (1-7.5 mg/kg) significantly increases the time spent in the drug-paired compartment in a dose-dependent manner. Intraperitoneal administration of agmatine (1-40 mg/kg) alone does not induce either CPP or conditioned place aversion, while combination of agmatine and subeffective doses of morphine leads to potent rewarding effects. Lower doses of morphine (0.1, 0.05, and 0.01 mg/kg) are able to induce CPP in mice pretreated with agmatine 1, 5, and 10 mg/kg, respectively. Concomitant intraperitoneal administration of UK 14 304 (0.5 mg/kg), a highly selective a 2 -agonist, with per se noneffective dose of morphine (0.5 mg/kg) and also its combination with noneffective doses of agmatine (1 mg/kg) plus morphine (0.05 mg/kg) produces significant CPP. UK 14 304 (0.05, 0.5 mg/kg) alone, or in combination with agmatine (1, 5 mg/kg) have had no effect. We have further investigated the possible involvement of the a 2 -adrenoceptors in the potentiating effect of agmatine on morphine-induced place preference. Selective a 2 -antagonists, yohimbine (0.005 mg/kg) and RX821002 (0.1, 0.5 mg/kg), block the CPP induced by concomitant administration of agmatine (5 mg/kg) and morphine (0.05 mg/kg). Yohimbine (0.001-0.05 mg/kg) or RX821002 (0.05-0.5 mg/kg) alone or in combination with morphine (0.05 mg/kg) or agmatine (5 mg/kg) fail to show any significant place preference or aversion. Our results indicate that pretreatment of animals with agmatine enhances the rewarding properties of morphine via a mechanism which may involve a 2 -adrenergic receptors.

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Section: Discussionmentioning

confidence: 99%

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Tahsili-Fahadan

Yahyavi-Firouz-Abadi

Khoshnoodi

et al. 2005

Neuropsychopharmacol

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“…Clonidine is an agonist at I1Rs in addition to a2Rs (Bricca et al, 1993;De Vos et al, 1994;Ernsberger et al, 1993Ernsberger et al, , 1987Michel et al, 1989;Wallace et al, 1994). To determine if the above actions were because of actions at a2ARs, we studied the effect of UK14304, a specific a2-adrenoreceptor agonist with an I1 binding site/a2 binding site affinity ratio o0.01 (Andorn et al, 1988;Bricca et al, 1993;Buccafusco et al, 1995;Urban et al, 1995).…”

Section: Costimulation Of A2-adrenergic Receptors and I1rs Is Requirementioning

confidence: 99%

“…To determine if the above actions were because of actions at a2ARs, we studied the effect of UK14304, a specific a2-adrenoreceptor agonist with an I1 binding site/a2 binding site affinity ratio o0.01 (Andorn et al, 1988;Bricca et al, 1993;Buccafusco et al, 1995;Urban et al, 1995). In contrast to the effects observed in morphine-dependent rats pretreated with clonidine, administration of UK14304 (0.1 mg/kg i.v.)…”

Section: Costimulation Of A2-adrenergic Receptors and I1rs Is Requirementioning

confidence: 99%

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

Georges

Aston‐Jones

2003

Neuropsychopharmacol

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The a2 adrenoceptor (a2R) agonist clonidine is used as a treatment for heroin addiction. Substantial evidence indicates that dopaminergic and noradrenergic systems have key roles in opiate dependence and withdrawal but the possible interactions between these two pathways remain unclear. The objective of this study was to establish the effects of clonidine pretreatment on ventral tegmental area dopaminergic (VTA DA) neuronal activity during morphine withdrawal. Responses of VTA DA neurons to withdrawal precipitated by naltrexone were characterized in anesthetized rats using extracellular recordings. As expected, withdrawal produced a marked inhibition of VTA DA neuronal activity. However, pretreatment with clonidine prevented this inhibition induced by withdrawal, and instead produced a long-lasting activation of firing rate (+50%) and burst firing (+19%). In contrast, pretreatment with a more selective a2R agonist, UK14304, did not prevent the inhibition of VTA DA neuron activity during withdrawal. We tested whether the high affinity of clonidine for imidazoline-1 receptors (I1Rs) was responsible for the difference between these two a2R agonists. In morphine-dependent rats pretreated with rilmenidine (mixed a2R/I1R agonist), precipitation of withdrawal elicited a 22% increase of VTA DA impulse activity. The action of clonidine on I1Rs was studied by coadministering clonidine with RX821002, a specific a2R antagonist. Pretreatment with RX821002 plus clonidine prevented the inhibition of VTA DA activity during withdrawal but failed to produce excitation. These results indicate that the pharmacological effects of clonidine on VTA DA neurons during morphine withdrawal is related to actions on I1Rs as well as a2Rs.

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“…Idazoxan is an imidazoline a 2 -adrenoceptor antagonist that also displays nanomolar anity for I 1 -imidazoline receptors (Bricca et al, 1993;Codd et al, 1995). Thus, the possible involvement of these receptors in mediating the eect of idazoxan was ®rst studied.…”

Section: Eects Of Idazoxan On the Antinociceptive Responses To Morphimentioning

confidence: 99%

“…The present study was, therefore, designed (1) to assess if idazoxan, an a 2 -adrenoceptor antagonist (Doxey et al, 1983) that also interacts with I 1 -and I 2 -imidazoline receptors (Bricca et al, 1993;Miralles et al, 1993) modulates opioid tolerance, (2) to establish which imidazoline receptor type or if other receptors (a 2 -adrenoceptors, NMDA receptors) could be implicated in the eects of idazoxan and (3) to assess if idazoxan and other I 2 -imidazoline ligands interfere with morphine-induced modulation of immunoreactive neuro®la-ment proteins. Idazoxan was chosen as the reference drug because of its current use in human clinical research (Schmidt et al, 1997a,b).…”

Section: Introductionmentioning

confidence: 99%

Attenuation of tolerance to opioid‐induced antinociception and protection against morphine‐induced decrease of neurofilament proteins by idazoxan and other I₂‐imidazoline ligands

Boronat

Olmos

Garcı́a-Sevilla

1998

British J Pharmacology

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1 Agmatine, the proposed endogenous ligand for imidazoline receptors, has been shown to attenuate tolerance to morphine-induced antinociception (Kolesnikov et al., 1996). The main aim of this study was to assess if idazoxan, an a 2 -adrenoceptor antagonist that also interacts with imidazoline receptors, could also modulate opioid tolerance in rats and to establish which type of imidazoline receptors (or other receptors) are involved. 2 Antinociceptive responses to opioid drugs were determined by the tail-¯ick test. The acute administration of morphine (10 mg kg 71 , i.p., 30 min) or pentazocine (10 mg kg 71 , i.p., 30 min) resulted in marked increases in tail-¯ick latencies (TFLs). As expected, the initial antinociceptive response to the opiates was lost after chronic (13 days) treatment (tolerance). When idazoxan (10 mg kg 71 , i.p.) was given chronically 30 min before the opiates it completely prevented morphine tolerance and markedly attenuated tolerance to pentazocine (TFLs increased by 71 ± 143% at day 13). Idazoxan alone did not modify TFLs. 3 The concurrent chronic administration (10 mg kg 71 , i.p., 13 days) of 2-BFI, LSL 60101, and LSL 61122 (valldemossine), selective and potent I 2 -imidazoline receptor ligands, and morphine (10 mg kg 71 , i.p.), also prevented or attenuated morphine tolerance (TFLs increased by 64 ± 172% at day 13). This attenuation of morphine tolerance was still apparent six days after discontinuation of the chronic treatment with LSL 60101-morphine. The acute treatment with these drugs did not potentiate morphineinduced antinociception. These drugs alone did not modify TFLs. Together, these results indicated the speci®c involvement of I 2 -imidazoline receptors in the modulation of opioid tolerance. The potencies of the imidazolines idazoxan, RX821002 and moxonidine were similar, indicating a lack of relationship between potency on NMDA receptors and ability to attenuate opioid tolerance. These results suggested that modulation of opioid tolerance by idazoxan is not related to NMDA receptors blockade. 6 Chronic treatment (13 days) with morphine (10 mg kg 71 , i.p.) was associated with a marked decrease (49%) in immunolabelled neuro®lament proteins (NF-L) in the frontal cortex of morphine-tolerant rats, suggesting the induction of neuronal damage. Chronic treatment (13 days) with idazoxan (10 mg kg 71 ) and LSL 60101 (10 mg kg 71 ) did not modify the levels of NF-L proteins in brain. Interestingly, the concurrent chronic treatment (13 days) of idazoxan or LSL 60101 and morphine, completely reversed the morphine-induced decrease in NF-L immunoreactivity, suggesting a neuroprotective role for these drugs. 7 Together, the results indicate that chronic treatment with I 2 -imidazoline ligands attenuates the development of tolerance to opiate drugs and may induce neuroprotective eects on chronic opiate treatment. Moreover, these ®ndings oer the I 2 -imidazoline ligands as promising therapeutic coadjuvants in the management of chronic pain with opiate drugs.

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Relevance of the use of [³H]‐clonidine to identify imidazoline receptors in the rabbit brainstem

Cited by 38 publications

References 41 publications

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

Attenuation of tolerance to opioid‐induced antinociception and protection against morphine‐induced decrease of neurofilament proteins by idazoxan and other I₂‐imidazoline ligands

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Relevance of the use of [3H]‐clonidine to identify imidazoline receptors in the rabbit brainstem

Cited by 38 publications

References 41 publications

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

Attenuation of tolerance to opioid‐induced antinociception and protection against morphine‐induced decrease of neurofilament proteins by idazoxan and other I2‐imidazoline ligands

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Relevance of the use of [³H]‐clonidine to identify imidazoline receptors in the rabbit brainstem

Attenuation of tolerance to opioid‐induced antinociception and protection against morphine‐induced decrease of neurofilament proteins by idazoxan and other I₂‐imidazoline ligands