Elsevier

Neuroscience Letters

Volume 494, Issue 2, 25 April 2011, Pages 169-173
Neuroscience Letters

Effect of the histone deacetylase inhibitors on behavioural sensitization to a single morphine exposure in mice

https://doi.org/10.1016/j.neulet.2011.03.005Get rights and content

Abstract

Behavioural sensitization to a single morphine exposure has been considered to be a long-term form of behavioural plasticity associated with opioid addiction. Accumulated evidence has shown that histone modification plays a key role in behavioural plasticity. Therefore, this study was designed to investigate whether the histone deacetylase inhibitors sodium butyrate (SB) and valproic acid (VPA) could disrupt behavioural sensitization to a single morphine exposure. Mice were pretreated with a single injection of morphine and elicited subsequent behavioural sensitization by a challenge-dosage of morphine after a 7-day drug-free period. At doses that did not affect the locomotor activity, both SB and VPA inhibited the acute morphine induced hyperactivity and significantly attenuated the development of behavioural sensitization to a single morphine exposure. Furthermore, the combination of SB and VPA at the sub-effective doses could additionally reduce the development of morphine sensitization. Western blot analysis revealed that multiple administration with the effective dose of SB (160 mg/kg, i.p.) or VPA (150 mg/kg, i.p.) in the behavioural experiments induced hyperacetylation of histone H3 in the NAc of mice. Taken together, these findings suggest that histone acetylation may be involved in morphine sensitization.

Highlights

► A single morphine-induced behavioural sensitization is simple and convenient. ► Reveal mechanisms of histone acetylation on development of morphine sensitization. ► HDACs in rodents may regulate drug addiction-related behaviours. ► Open a new potential way toward treating drug abuse and dependence.

Section snippets

Acknowledgements

This work was supported by grants from National Nature Science Foundation of China (Nos. 30570653 and 30870894), National Basic Research Program of China (Nos. 2003CB515400 and 2009CB522000), 985 Program of China Ministry of Education (State Key Laboratory of Natural and Biomimetic Drugs, Peking University) and Tianjin Medical University Science Foundation of China (No. 2010ky02). A.J.L. is a Senior Fellow supported by the National Health & Medical Research Council (Australia).

References (31)

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