The extinction of morphine-induced conditioned place preference by histone deacetylase inhibition.
Recent evidence suggests that epigenetic mechanisms have an important role in the development of addictive behavior. However, little is known about the role of epigenetic mechanisms in the extinction of morphine-induced behavioral changes. In this study, we will examine the effect of histone deacetylase (HDAC) inhibitors on extinction of morphine-induced conditioned place preference (CPP). To facilitate extinction, rats will be administered an HDAC inhibitor (HDACi) following nonreinforced exposure to the conditioned context. To measure persistence, rats were subject to a reinstatement test using 3 mg/kg dose of morphine. To exclude the effect of repeated NaBut injections themselves on morphine-CPP in the absence of extinction session, rats received injection of either NaBut or vehicle for 8 days. We found that HDAC inhibition during nonconfined extinction or confined extinction consolidation can facilitate extinction of morphine-induced CPP. We also showed that the extinction of drug seeking via HDAC inhibition modulates extinction learning such that reinstatement behavior is significantly attenuated. There is no effect of repeated NaBut injections themselves on morphine-CPP in the absence of extinction session. In conclusion, our results extend earlier reports on the ability of HDACi to modify the behavioral effects of drugs of abuse. Our increasing understanding of these epigenetic mechanisms will provide key answers to basic processes in drug addiction and hopefully provide insight into designing improved treatments for drug addiction.
Wang
Ru
R
Department of Pharmacy, Tangdu Hospital, The Fourth Military Medical University, Ba Qiao District, Xi'an, Shaanxi, China.
Zhang
Yan
Y
Qing
Hua
H
Liu
Mei
M
Yang
Peng
P
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D009020:Morphine; C515890:Hdac1 protein, rat; D056284:Histone Deacetylase 1