期刊
NEUROSCIENCE
卷 258, 期 -, 页码 101-110出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2013.11.025
关键词
levo-tetrahydropalmatine; methamphetamine; locomotor sensitization; extracellular-regulated kinase
资金
- Ministry of Science and Technology of China [2009 DFA 31080]
- National Natural Science Foundation of China [81172913]
Levo-tetrahydropalmatine (l-THP) is an alkaloid purified from corydalis and has been used in many traditional Chinese herbal preparations for its analgesic, sedative, and hypnotic properties. Previous studies indicated that l-THP has modest antagonist activity against dopamine receptors and thus it might have potential therapeutic effects on drug addiction. However, whether and how l-THP contributes to methamphetamine (METH)-induced locomotor sensitization remains unclear. Therefore, the current study aims to examine the roles of l-THP in the development and expression of METH-induced locomotor sensitization as well as the accompanying extracellular-regulated kinase (ERK) activation in the nucleus accumbens (NAc), caudate putamen (CPu) and prefrontal cortex (PFc) in mice. We found that moderate doses of METH (0.5 and 2 mg/kg) induced hyper-locomotor activity in mice on all METH injection days whereas high dose of METH (5 mg/kg)-treated mice displayed only acute locomotor response to METH and severe stereotyped behaviors on the first day after drug injection. Interestingly, only 2 mg/kg dose of METH-induced locomotor sensitization which was accompanied by the activation of ERK1/2 in the NAc and CPu in mice. Although l-THP (5 and 10 mg/kg) per se did not induce obvious changes in locomotor activities in mice, its coadministration with METH could significantly attenuate acute METH-induced hyper-locomotor activity, the development and expression of METH-induced locomotor sensitization, and the accompanying ERK1/2 activation in the NAc and CPu. These results suggest that l-THP has potential therapeutic effect on METH-induced locomotor sensitiza-tion, and the underlying molecular mechanism might be related to its inhibitory effect on ERK1/2 phosphorylation in the NAc and CPu. (C) 2013 Published by Elsevier Ltd. on behalf of IBRO.
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