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Effect of Histone Acetylation on Maintenance and Reinstatement of Morphine-Induced Conditioned Place Preference and Δfosb Expression in the Nucleus Accumbens and Prefrontal Cortex of Male Rats Publisher Pubmed



Saberian H1 ; Asgari Taei A1 ; Torkamanboutorabi A1 ; Riahi E2 ; Aminyavari S1 ; Naghizadeh A3 ; Farahmandfar M1
Authors
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Authors Affiliations
  1. 1. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Behavioural Brain Research Published:2021


Abstract

Recently, epigenetic mechanisms are considered as the new potential targets for addiction treatment. This research was designed to explore the effect of histone acetylation on ΔFosB gene expression in morphine-induced conditioned place preference (CPP) in male rats. CPP was induced via morphine injection (5 mg/kg) for three consecutive days. Animals received low-dose theophylline (LDT) or Suberoylanilide Hydroxamic acid (SAHA), as an histone deacetylase (HDAC) activator or inhibitor, respectively, and a combination of both in subsequent extinction days. Following extinction, a priming dose of morphine (1 mg/kg) was administered to induce reinstatement. H4 acetylation and ΔFosB expression in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were assessed on the last day of extinction and the following CPP reinstatement. Our results demonstrated that daily administration of SAHA (25 mg/kg; i.p.), facilitated morphine-extinction and decreased CPP score in reinstatement of place preference. Conversely, injections of LDT (20 mg/kg; i.p.) prolonged extinction in animals. Co-administration of LDT and SAHA on extinction days counterbalanced each other, such that maintenance and reinstatement were no different than the control group. The gene expression of ΔFosB was increased by SAHA in NAc and mPFC compared to the control group. Administration of SAHA during extinction days, also altered histone acetylation in the NAc and mPFC on the last day of extinction, but not on reinstatement day. Collectively, administration of SAHA facilitated extinction and reduced reinstatement of morphine-induced CPP in rats. This study confirms the essential role of epigenetic mechanisms, specifically histone acetylation, in regulating drug-induced plasticity and seeking behaviors. © 2021
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