Effects of group I metabotropic glutamate receptor antagonist on expression of pCREB in the spinal cord of morphine-tolerant rats

Objective To observe the effects of group I metabotropic glutamate receptor antagonist on the expression of phosphated cAMP response element-binding protein(pCREB) in the spinal cord of morphine-tolerant rats.Methods Male SD rats were randomly divided into four groups with 6 rats each:morphine group(M),AIDA group(A),morphine plus AIDA group(MA) and control group(C).Drugs were administrated intrathecally twice a day for 8 consecutive days.Tail flick latency(TFL) was measured and MPE%(percentage of maximal possible effect) was calculated according to the equation.The rats were killed on the day after last intrathecal administration.The expression of pCREB protein was assessed by Western blot method.Results MPE% of group M and MA was significantly higher than that of group C(P 0.01) on the 1st and 2nd day,but the effect of analgesia in group M was gradually decreased on the later days.There was no significant difference between group M and C on the 7th day.Group MA had significant analgesic effect compared with group M from the 3rd to 8th day(P0.01).MPE% was significantly higher in group MA than that in group C and group A during eight days.The protein level of pCREB in group M was higher than that in the other three groups(P0.01).The protein level in group MA was higher than that in group C(P0.05),but much lower than that in group M(P0.01).Conclusion Expression of pCREB is upregulated during morphine tolerance.AIDA partly blocks the development of morphine tolerance by inhibiting the expression of pCREB.