Original Article

The small GTPase RhoA, but not Rac1, is essential for conditioned aversive memory formation through regulation of actin rearrangements in rat dorsal hippocampus

Jun Wang, Yu-hua Wang, Yuan-yuan Hou, Tao Xi, Yao Liu, Jing-gen Liu
DOI: 10.1038/aps.2013.3


Jun WANG1, Yu-hua WANG1, 3, Yuan-yuan HOU2, Tao XI1, *, Yao LIU2, *, Jing-gen LIU2
1Biotechnology Center, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China; 2State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China; 3School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China

Aim: Actin rearrangements are induced in the dorsal hippocampus after conditioned morphine withdrawal, and involved in the formation of conditioned place aversion. In the present study, we investigated the mechanisms underlying the actin rearrangements in rat dorsal hippocampus induced by conditioned morphine withdrawal.
Methods: The RhoA-ROCK pathway inhibitor Y27632 (8.56 μg/1 μL per side) or the Rac1 inhibitor NSC23766 (25 μg/1 μL per side) was microinjected into the dorsal hippocampus of rats. Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal was assessed. Crude synaptosomal fraction of hippocampus was prepared, and the amount of F-actin and G-actin was measured with an Actin Polymerization Assay Kit.

Results: Conditioned morphine withdrawal significantly increased actin polymerization in the dorsal hippocampus at 1 h following the naloxone injection. Preconditioning with microinjection of Y27632, but not NSC23766, attenuated CPA, and blocked the increase in actin polymerization in the dorsal hippocampus.

Conclusion: Our results suggest that the small GTPase RhoA, but not Rac1, in the dorsal hippocampus is responsible for CPA formation, mainly through its regulation of actin rearrangements.

Keywords: morphine withdrawal; aversive memory; conditioned place aversion; dorsal hippocampus; actin rearrangement; RhoA; Rac1; naloxone; Y27632; NSC23766

This research was supported by the National Basic Research Program grant from the Ministry of Science and Technology of China 2009CB522005 (Jing-gen LIU), as well as grants from the Foundation of National Natural Science of China 81130087 (Jing-gen LIU), 81001424 (Yuan-yuan HOU) and the Foundation of Natural Science of Jiangshu Province SBK201241521 (Yu-hua WANG).

* To whom correspondence should be addressed.
E-mail xi-tao18@hotmail.com (Tao XI); liuyaowuhan@163.com (Yao LIU)
Received 2012-10-23 Accepted 2013-01-11

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