Down-regulation of MAO-B activity and imidazoline receptors in rat brain following chronic treatment of morphine

AIM: To study the regulation of monoamine oxidase-B (MAO-B) activity and im idazoline 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 [H-3]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 activi ty of MAO-B, and it had no effect on the inhibition of MAO-B activity by id azoxan or morphine. MAO-B activity of rats decreased markedly in all five b rain 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 didn't influence MAO-B activity i n morphine chronically treated rats. Although agmatine itself didn't affect MAO-B activity, co-administration of agmatine with morphine could reverse the effect of morphine on MAO-B activity. Chronic administration of morphin e significantly decreased the density of [H-3] idazoxan binding sites and i ncreased the binding affinity in cerebral cortex and cerebellum (P < 0.05 o r P < 0.01). CONCLUSION: MAO-B activity was relevant to the abstinent syndr ome of morphine dependent rats, but not related to the effect of agmatine o n morphine analgesia; influence of agmatine on the pharmacological effects of morphine was based on its activation of imidazoline receptors.