Authors: Florence R M Theberge Charles L Pickens Evan Goldart Sanya Fanous Bruce T Hope QingRong Liu Yavin Shaham
Publish Date: 2012/07/12
Volume: 224, Issue: 4, Pages: 559-571
Abstract
Responding to heroin cues progressively increases after cessation of heroin selfadministration incubation of heroin craving We investigated whether this incubation is associated with timedependent changes in brainderived neurotrophic factor BDNF and methylCpG binding protein 2 MeCP2 signaling and mu opioid receptor MOR expression in nucleus accumbens NAc dorsal striatum DS and medial prefrontal cortex mPFC We also investigated the effect of the preferential MOR antagonist naloxone on cueinduced heroin seeking during abstinenceWe trained rats to selfadminister heroin or saline for 9–10 days and then dissected the NAc DS and mPFC at different abstinence days and measured mRNA and protein levels of BDNF TrkB and MeCP2 as well as MOR mRNA Oprm1 In other groups we assessed cueinduced heroin seeking in extinction tests after 1 11 and 30 abstinence days and naloxone’s 0–10 mg/kg effect on extinction responding after 1 and 15 daysCueinduced heroin seeking progressively increased or incubated during abstinence This incubation was not associated with changes in BDNF TrkB or MeCP2 mRNA or protein levels in NAc DS or mPFC additionally no molecular changes were observed after extinction tests on day 11 In NAc but not DS or mPFC MOR mRNA decreased on abstinence day 1 and returned to basal levels over time Naloxone significantly decreased cueinduced heroin seeking after 15 abstinence days but not 1 dayResearch was supported by the National Institute on Drug Abuse’s Intramural Research Program We thank Xingyu Hou for helping with the molecular assays and Brittany Navarre and Anna Stern for helping with the intravenous surgeries We also thank Dr Anne E West Duke University for helpful comments on the molecular aspects of our work The authors declare that they do not have any conflicts of interest financial or otherwise related to the data presented in this manuscript
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