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


CONCLUSIONS
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.
Su
R B
RB
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Li
J
J
Li
X
X
Qin
B Y
BY
D000376:Agmatine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D015536:Down-Regulation; D019329:Idazoxan / Q000494:pharmacology; D054755:Imidazoline Receptors; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000378:metabolism*
D054755:Imidazoline Receptors; D011955:Receptors, Drug; D000376:Agmatine; D009020:Morphine; D008995:Monoamine Oxidase; D019329:Idazoxan