Effect of chronic morphine treatment on the biosynthesis of agmatine in rat brain and other tissues

Aricioglu-Kartal, F.; Regunathan, S.

doi:10.1016/s0024-3205(02)01911-2

Cited by 37 publications

(19 citation statements)

References 21 publications

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“…Agmatine prevents naloxone-precipitated abstinence syndrome in morphine-dependent rats and attenuates all of the signs of morphine withdrawal syndrome dose-dependently (Aricioglu-Kartal and Uzbay, 1997;Uzbay et al, 2000;Li et al, 2002;Aricioglu et al, 2004). Exposure of rats to morphine for 3 days is shown to decrease the levels of agmatine in the liver, kidney, brain, aorta, and intestine; also, precipitation of withdrawal syndrome by injecting naloxone further decreases agmatine levels in these tissues, providing evidence that endogenous agmatine may play an important role in regulating morphine tolerance, dependence, and withdrawal symptoms (Aricioglu-Kartal and Regunathan, 2002). Moreover, substances involved in the metabolism of endogenous agmatine, such as aminoguanidine and a-difluoromethylornithine, could modulate the pain threshold, morphine analgesia, and tolerance (Lu et al, 2003).…”

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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“…Additionally, compared to both the morphine-treated and control groups, similar findings occurred in the rats that were induced to withdraw. Thus, their data suggest that morphine affects tissue and plasma levels of endogenous agmatine by reducing agmatine synthesis [7].…”

Section: Discussionmentioning

confidence: 99%

“…Aricioglu-Kartal F and Regunathan S [7,8] were among the first to demonstrate the effects of opioid administration on endogenous agmatine metabolism. They examined the effects of agmatine metabolism in rats where they had an animal control group, a group with "chronic" (3 days) exposure to morphine and a group with chronic morphine exposure who were then induced to withdrawal.…”

Section: Discussionmentioning

confidence: 99%

“…To the best of our knowledge, the variation of plasma agmatine concentrations over time are unknown in both animals and humans. Agmatine is found to have multiple roles in mammals but the majority of studies have primarily involved animals and focused on the distribution of agmatine in the various tissues of the body and its potential role in these tissues [3][4][5][6][7][13][14][15][16][17][18][19]. The brain has been a major area of interest as agmatine's role is believed to be that of a neurotransmitter based on its concentration, distribution, presence and function in the CNS [8].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous animal studies demonstrated that administration of exogenous agmatine prevents the occurence of opioid tolerance and dependence and abates the occurrence of withdrawal [3][4][5][6]. In animal studies, endogenous agmatine levels are influenced by chronic morphine exposure and induction of withdrawal, suggesting an important role in the regulation of opioid tolerance, dependence, and withdrawal [7].…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Fentanyl Administration on Plasma Agmatine Concentration In Critically Ill Patients

Castro¹

2015

JPNC

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Background: Agmatine, a product of L-arginine metabolism, has been shown to influence opioid tolerance, dependence and withdrawal in animal studies. The purpose of this study was to characterize the plasma agmatine concentration of critically ill, mechanically ventilated patients receiving continuous fentanyl infusion as part of their sedation/analgesia regimen. We hypothesized that these patients would demonstrate lower plasma agmatine levels.Methods: All admissions to our pediatric intensive care unit (PICU) who received mechanical ventilation and fentanyl infusions as part of their sedation/analgesia regimen were eligible. Plasma agmatine concentrations were correlated with patient demographics and medication administration data.Results: Twenty two mechanically ventilated children were enrolled and showed a negative correlation between Δ plasma agmatine concentration and the COMFORT score (r=-0.42, p<0.01), Δ cumulative fentanyl dose (r=-0.48, p<0.01), Δ fentanyl infusion rate (r=-46, p<0.01), and fentanyl infusion duration (r=-37, p<0.01).Conclusions: Mechanically ventilated, critically ill patients receiving prolonged opioid infusions and meeting the definition of tolerance demonstrated lower plasma agmatine concentrations relative to baseline.

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An ethopharmacological assessment of agmatine's effects on agonistic encounters between male mice

Navarro

Luna

2005

Aggr. Behav.

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The endogenous polyamine agmatine may be a new central neurotransmitter. Agmatine-like immunoreactivity has been described in numerous brain regions (such as the hypothalamus and amygdala), long thought involved in the control of aggression. Consequently, the present study examined agmatine's (2.5-80 mg/kg, ip) effects on behavior directed by isolated male mice to anosmic partners in a neutral area. The videotaped encounters were analysed in terms of 10 broad behavioral categories. Agmatine did not appear to be involved in the modulation of aggression or anxiety in this test. Aggr. Behav. 31:374-380, 2005. r

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Effect of chronic morphine treatment on the biosynthesis of agmatine in rat brain and other tissues

Cited by 37 publications

References 21 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

The Effect of Fentanyl Administration on Plasma Agmatine Concentration In Critically Ill Patients

An ethopharmacological assessment of agmatine's effects on agonistic encounters between male mice

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