Role of spinal cord proteasome in chronic morphine tolerance in rats
10.3760/cma.j.issn.0254-1416.2011.07.018
- VernacularTitle:脊髓蛋白酶体在大鼠慢性吗啡耐受形成中的作用
- Author:
Yanping WANG
;
Yunfei SUN
;
Yonghao YU
- Publication Type:Journal Article
- Keywords:
Proteasome endopeptidase complex;
Spinal cord;
Drug tolerance;
Morphine
- From:
Chinese Journal of Anesthesiology
2011;31(7):837-839
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo evaluate the role of the spinal cord proteasome in chronic morphine tolerance in rats.MethodsTwenty-four healthy male SD rats in which intrathecal catheters were successfully placed without complications were randomized into 4 groups ( n =6 each):normal saline group ( group NS),chronic morphine tolerance group (group M),chronic morphine tolerance + proteasome inhibitor MG-132 group (group M + MG) and MG-132 group (group MG).Normal saline 10 μl,morphine 10 μg,morphine 10 μg+ MG-132 2.5 μg and MG-132 2.5 μg were injected intrathecally twice a day for 7 consecutive days in groups NS,M,M + MG and MG respectively.Tail flick latency was measured on day 1 before intrathecal injection and on day 1,3,5 and 7 of intrathecal injection to calculate the percentage of maximum possible antinociceptive effect (MPAE).After the last intrathecal injection,5 rats were sacrificed,and L3-5 spinal cord was removed for determination of the expression of glutamate-aspartate transporter (GLAST) and excitatory amino acids carrier 1 (EAAC1)by Western blot.Results MPAE was gradually decreased during the intrathecal injection in groups M and M + MG( P < 0.05).Compared with group NS,MPAE was gradually incresed during the intrathecal injection in groups M and M + MG,and the expression of GLAST and EAAC1 in the spinal cord was significantly down-regulated in group M (P < 0.05).There was no significant difference in the parameters mentioned above between group MG and group NS ( P >0.05 ).Compared with group M,MPAE was significantly increased and the expression of GLAST and EAAC1 in the spinal cord was significantlyup-regulatedingroupM+MG(P<0.05or0.01).ConclusionSpinal cord proteasome is involved in the development of chronic morphine tolerance in rats.