REGULAR ARTICLES

Cell Research (2003); 13(1):29-34

Ohmefentanyl stereoisomers induce changes of CREB phosphorylation in hippocampus of mice in conditioned place preference paradigm

Can GAO^1,2, Li Wei CHEN¹, Jie CHEN¹, Xue Jun XU¹, Zhi Qiang CHI^1,*

¹Second Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
²Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China

Corresponding author: Prof. Zhi Qiang CHI Second Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China Tel: 86-21-64311833 ext 513,  Fax: 86-21-64370269, E-mail: zqchi@mail.shcnc.ac.cn

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Abstract

The present study was designed to determine the changes of phosphorylation of cAMP- response element binding protein (CREB) in hippocampus induced by ohmefentanyl stereoisomers (F9202 and F9204) in conditioned place preference (CPP) paradigm. The results showed that mice receiving F9202 and F9204 displayed obvious CPP. They could all significantly stimulate CREB phosphorylation and maintained for a long time without affecting total CREB protein levels. The effect of F9204 was similar to morphine which effect was more potent and longer than F9202. We also examined the effects of ketamine, a noncompetitive N-mthyl-D-aspartate receptor (NR) antagonist, on morphine-, F9202- and F9204- induced CPP and phosphorylation of CREB in hippocampus. Ketamine could suppress not only the place preference but also the phosphorylation of CREB produced by morphine, F9202 and F9204. These findings suggest that alterations in the phosphorylation of CREB be relevant to opiates signaling and the development of opiates dependence. NR antagonists may interfere with opiates dependence and may have potential therapeutic implications.

Key words: cAMP-response element binding protein (CREB), ohmefentanyl stereo isomers, opiates, hippocampus, conditioned place preference (CPP).