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  • Title: Down-regulation of MAO-B activity and imidazoline receptors in rat brain following chronic treatment of morphine.
    Author: Su RB, Li J, Li X, Qin BY.
    Journal: Acta Pharmacol Sin; 2001 Jul; 22(7):639-44. PubMed ID: 11749830.
    Abstract:
    AIM: To study the regulation of monoamine oxidase-B (MAO-B) activity and imidazoline receptors (I-R) during long term treatment of morphine. METHODS: MAO-B activity was detected by high performance liquid chromatography; I-R was detected by [3H]idazoxan binding test. RESULTS: Idazoxan and morphine inhibited whole brain homogenate MAO-B activity in a dose-dependent manner, while agmatine, an endogenous imidazoline ligand, didn't affect the activity of MAO-B, and it had no effect on the inhibition of MAO-B activity by idazoxan or morphine. MAO-B activity of rats decreased markedly in all five brain regions detected (cerebral cortex, hippocampus, thalamus, cerebellum, and striatum) after chronic administration of morphine for 16 d (P < 0.01). Acute challenge with naloxone or idazoxan did not influence MAO-B activity in morphine chronically treated rats. Although agmatine itself did not affect MAO-B activity, co-administration of agmatine with morphine could reverse the effect of morphine on MAO-B activity. Chronic administration of morphine significantly decreased the density of [3H]idazoxan binding sites and increased the binding affinity in cerebral cortex and cerebellum (P < 0.05 or P < 0.01). CONCLUSION: MAO-B activity was relevant to the abstinent syndrome of morphine dependent rats, but not related to the effect of agmatine on morphine analgesia; influence of agmatine on the pharmacological effects of morphine was based on its activation of imidazoline receptors.
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