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

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.