Changes in 20S proteasome acitivities in brain and spinal cord of acute and chronic morphine-dependent mice

Abstract

Objective To investigate the changes in 20S proteasome activities in the brain and spinal cord of acute and chronic morphine-dependent mice. Methods Male ICR mice, weighing 25-30 g, were used in the study.The experiment was performed in 2 parts.In experiment Ⅰ, 16 mice were randomly divided into 5 groups (n=8 each) using a random number table: control group (group C) and acute morphine dependence group (AMD group). In experiment Ⅱ, 16 mice were randomly divided into 5 groups (n=8 each) using a random number table: control group (group C) and chronic morphine dependence group (CMD group). Acute morphine dependence was induced with morphine 100 mg/kg injected subcutaneously, and the mice were sacrificed 3 h later.Chronic morphine dependence was induced by increasing doses of morphine for 4 days, the initial dose of morphine was 20 mg/kg injected subcutaneously twice a day and was increased by 10 mg/kg every day, the dose of morphine was 10 mg/kg injected subcutaneously on 5th day, and then the mice were sacrificed 1 h later.In group C, the equal volume of normal saline was given instead, and the other treatments were similar to those previously described in morphine dependence groups.After the mice were sacrificed, the hippocampus, prefrontal cortex, striatum and spinalcord were isolated for determination of 20S proteasome activity, measured as chymotrypsin-like (ChT-L), trypsin-like (T-L) and peptidylglutamyl-like hydrolyzing (PGLH) activities. Results ExperimentⅠ Compared with C group, PGLH activity in the spinal cord and T-L activity in the striatum or prefrontal cortex were significantly weakened in group AMD.There was no significant difference in 20S proteasome activity in the hippocampus between the two groups.Experiment Ⅱ Compared with C group, ChT-L and T-L activities in the spinal cord were significantly weakened, and PGLH activity in the striatum was enhanced in CMD group.There was no significant difference in 20S proteasome activity in the prefrontal cortex and hippocampus between the two groups. Conclusion 20S proteasome activity in the spinal cord and brain is weakened in acute morphine-dependent mice, 20S proteasome activity in the spinal cord is weakened, 20S proteasome activity in the striatum is enhanced in chronic morphine-dependent mice, these changes have specificity in terms of position and type of activity, and the changes mentioned above may be related to development of morphine dependence in mice. Key words: Morphine dependence; Substance withdrawal syndrome; Proteasome endopepti-dase complex; Spinal cord; Brain