Regulation of histone acetylation by garcinol blocks the reconsolidation of heroin-associated memory

Abstract

Drug-associated long-term memories underlie substance use disorders, including heroin use disorder (HUD), which are difficult to eliminate through existing therapies. Addictive memories may become unstable when reexposed to drug-related cues and need to be stabilized again through protein resynthesis. Studies have shown the involvement of histone acetylation in the formation and reconsolidation of long-term drug-associated memory. However, it remains unknown whether and how histone acetyltransferases (HAT), the essential regulators of histone acetylation, contribute to the reconsolidation of heroin-associated memories. Herein, we investigated the function of HAT in the reconsolidation concerning heroin-conditioned memory by using a rat self-administration model. Systemic administration of the HAT inhibitor garcinol inhibited cue and heroin-priming induced reinstatement of heroin seeking, indicating the treatment potential of garcinol for relapse prevention.

Keywords: Garcinol; Heroin; Histone acetylation; Reconsolidation; Reinstatement.