IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Clin Exp Med 2013;6(7):540-545

Original Article
Neuronal apoptosis in morphine addiction and its molecular mechanism

Li-Wei Liu, Jun Lu, Xin-Hua Wang, Shu-Kun Fu, Quan Li, Fu-Qing Lin

Department of Anesthesiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China; Department
of Anesthesiology, East Hospital, Tongji University School of Medicine, Shanghai, China. Li-Wei Liu and Jun Lu contributed equally.
Received May 23, 2013; Accepted June 25, 2013; Epub August 1, 2013; Published August 15, 2013

Abstract: Objective: This study aimed to investigate neuronal apoptosis and expression of apoptosis related proteins (Fas, Caspase-3
and Bcl-2) in the brain of rates with morphine addiction. Methods: A total of 48 adult male Sprague-Dawley rats weighing 190-210 g
were randomly divided into 3 groups (n=16 per group): morphine addiction group, morphine abstinence group and control group. Rats
in the addiction group and the abstinence group were intraperitoneally treated with morphine for 13 days to induce morphine addiction.
In abstinence group, rats were then intraperitoneally treated with naloxone at 5 mg/kg to induce abstinence for 30 min. Rats in the
control group were injected with normal saline. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was
employed to detect apoptotic cells. Immunohistochemistry and Western blot assay were performed to determine the expressions of
Fas, Bcl-2 and Caspase-3 in the hippocampus. Results: When compared with the control group, the proportion of apoptotic neurons
increased significantly in the addiction group and the abstinence group (P<0.01), accompanied by significantly increased expressions
of Fas and Caspase-3 (P<0.01) and markedly decreased Bcl-2 expression (P<0.01) in the hippocampuse. However, no significant
differences were observed between the addiction and the abstinence group (P>0.05). Conclusion: Long term use of morphine can
induce neuronal apoptosis in the brain by increasing the expressions of pro-apoptotic Fas and Caspase-3 and decreasing the anti-
apoptotic Bcl-2 expression, which might be one of mechanisms underlying the opiate-induced neuronal damage. (IJCEM1305015).

Keywords: Morphine addiction, hippocampus, apoptosis, Fas, Bcl-2, Caspase-3

Address correspondence to: Fu-Qing Lin, Department of Anesthesiology, Shanghai Tenth People’s Hospital, Tongji University School
of Medicine, Shanghai, China. E-mail: linfuqing321@yeah.net