Different modulation of mu opioid receptor induced by acute and chronic morphine dependence in rat brain / 中华麻醉学杂志

ABSTRACT

Objective To investigate the different changes in the regulation and gene expression of mu opioid receptor (MOR) in rat brain after acute and chronic morphine dependence.Methods Forty male SD rats weighing (210?35)g were randomly divided into five equal groups of eight animals each (1) control; (2) acute dependence (3) chronic dependence;(4) acute abstinence; (5) chronic abstinence. In acute dependence group rats received eight consecutive subcutaneous injection of morphine 5mg?kg-1 at 2h interval. In chronic dependence group morphine was injected subcutaneously three times a day(800, 15 00, 2200) for six days. The doses of morphine were 5, 10, 20, 40, 50, 60 mg? kg-1?day-1 from the 1st day to the 6th day respectively. In the two abstinence groups, the withdrawal syndromes were induced by intraperitoneal naloxone 5 mg ? kg-1. The rats in control group received saline. 30 min after the end of all procedures the animals were decapitated on ice. Brain was removed immediately and kept in liquid nitrogen. The Bmax and Kd values of 3H-DAMGO saturation binding to MOR were measured by Scatchard analysis. The gene expression of MOR was appraised by RT-PCR. Results (1) In the acute dependence group the Bmax value(the specific binding capacity of MOR) significantly increased and the affinity decreased. After abstinence the Bmax value returned to normal, but the affinity was still low. In chronic dependence and abstinence groups Bmax value decreased significantly and there was no change in Kd value. (2) The level of MOR mRNA increased significantly in acute dependence group and returned rapidly to normal after abstinence . In chronic dependence and abstinence groups the transcription of MOR was significantly lower than in control group. Conclusions The modulation of MOR in rat brain is different between acute and chronic dependence and there must be similar post-receptor mechnism involved.