Agmatine potentiates morphine-induced conditioned place preference in mice: modulation by alpha2-adrenoceptors.
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 alpha2-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 alpha2-adrenoceptors in the potentiating effect of agmatine on morphine-induced place preference. Selective alpha2-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 alpha2-adrenergic receptors.
Tahsili-Fahadan
Pouya
P
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Yahyavi-Firouz-Abadi
Noushin
N
Khoshnoodi
Mohammad Ali
MA
Motiei-Langroudi
Rouzbeh
R
Tahaei
Seyed Amir
SA
Ghahremani
Mohammad Hossein
MH
Dehpour
Ahmad Reza
AR
D000322:Adrenergic Agonists / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*
D000322:Adrenergic Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D000376:Agmatine; D009020:Morphine