Inhibition of Histone Deacetylases Facilitates Extinction and Attenuates Reinstatement of Nicotine Self-Administration in Rats

Castino, Matthew R.; Cornish, Jennifer L.; Clemens, Kelly J.

doi:10.1371/journal.pone.0124796

Cited by 29 publications

(32 citation statements)

References 40 publications

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“…Similar methods have been used by others (Berglind et al 2007; Castino et al 2015; Fuchs et al 1998, 2005; Venniro et al 2016). …”

Section: Methodsmentioning

confidence: 87%

“…One of few studies to investigate the effects of HDACi on operant drug extinction found that a post-extinction injection (IP) of a class I inhibitor (NaB) decreased nicotine-seeking during cued-extinction (one day after treatment), that at least six days of post-extinction treatment decreased the time it took to reach extinction criterion, and weakened reinstatement (Castino et al 2015). This effect supports our results with post-session delivery, with faster rates of extinction criterion reached in the RGFP966-treated rats compared to vehicle-treated rats in our studies.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, systemic and short-term application of RGFP966, a novel and selective HDAC3 inhibitor enhances histone acetylation (at H3K14 and H4K8) and extinction learning in mice, resulting in decreased drug-primed reinstatement after extinction of cocaine-induced conditioned place preference (CPP; Malvaez et al 2013). Although increases in learning and corresponding decreases in drug-seeking have been shown in Pavlovian and operant learning (Malvaez et al 2010; Castino et al 2015; Romieu et al 2008), no studies to date have determined the effects of targeting just one HDAC with extinction after drug self-administration.…”

Section: Introductionmentioning

confidence: 99%

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Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats

et al. 2018

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Rationale: A challenge in treating substance use disorder is that successful treatment often does not persist, resulting in relapse and continued drug seeking. One approach to persistently weaken drug-seeking behaviors is to pair exposure to drug-associated cues or behaviors with delivery of a compound that may strengthen the inhibition of the association between drug cues and behavior. Objectives: We evaluated whether a selective histone deacetylase 3 (HDAC3) inhibitor could promote extinction and weaken contextual control of operant drug-seeking after intravenous cocaine self-administration. Methods: Male Long Evans rats received a systemic injection of the HDAC3 inhibitor RGFP966 either before or immediately after the first extinction session. Persistence of extinction was tested over subsequent extinction sessions, as well as tests of reinstatement that included cue-induced reinstatement, contextual renewal, and cocaine-primed reinstatement. Additional extinction sessions occurred between each reinstatement test. We also evaluated effects of RGFP966 on performance and motivation during stable fixed ratio operant responding for cocaine and during a progressive ratio of reinforcement. Results: RGFP966 administered before the first extinction session led to significantly less responding during subsequent extinction and reinstatement tests compared to vehicle-injected rats. Follow-up studies found that these effects were not likely due to a performance deficit or a change in motivation to self-administer cocaine, as injections of RGFP966 had no effect on stable responding during a fixed or progressive ratio schedule. In addition, RGFP966 administered just after the first extinction session had no effect during early extinction and reinstatement tests, but weakened long-term responding during later extinction sessions. Conclusions: These results suggest that a systemic injection of a selective HDAC3 inhibitor can enhance extinction and suppress reinstatement after cocaine self-administration. The finding that behavioral and pharmacological manipulations can be combined to decrease drug-seeking provides further potential for treatment by epigenetic modulation.

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“…Similar methods have been used by others (Berglind et al 2007; Castino et al 2015; Fuchs et al 1998, 2005; Venniro et al 2016). …”

Section: Methodsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats

et al. 2018

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“…The current study shows that mice receiving NaB injections immediately after extinction trainings extinguished METH‐induced CPP both faster and to a greater extent than saline‐treated mice. It is important to emphasize that the extinction of CPP not only is involved in the extinction of already established addictive memory but also initiated the process of extinction memory, which also requires the activation of gene transcription (Alberini, ; Bouton et al, ; Castino et al, ). Therefore, a possible explanation for our results is that NaB facilitated the consolidation of extinction memory by enhancing the transcription of genes required for the formation of memory.…”

Section: Discussionmentioning

confidence: 99%

Sodium butyrate modulates a methamphetamine‐induced conditioned place preference

Zhu

Zhao

Chen

et al. 2016

J of Neuroscience Research

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Previous studies demonstrated that histone acetylation modulated the transcription of associated gene expression and thus contributed to the persistence of addictive behaviors and neuroplasticity. Nonetheless, the roles of histone acetylation in distinct phases of methamphetamine (METH)-induced conditioned place preference (CPP) remain unclear. The current study examines the effects of the histone deacetylases (HDACs) inhibitor sodium butyrate (NaB) on the acquisition, extinction, and reinstatement of METH-induced CPP in mice. Our results showed that 1 mg/kg METH induced CPP in mice after four conditioning sessions. METH-induced CPP was extinguished after three extinction training sessions and could be triggered by the same dose (1 mg/kg) of METH on the reinstatement test day. Meanwhile, NaB (400 mg/kg) per se had no effect on the natural preference of mice, but injections of NaB during the conditioning and extinction phases facilitated the acquisition and extinction of METH-induced CPP, respectively. Additionally, although the effect of a single NaB injection prior to the trigger of CPP reinstatement was not observed, repeated NaB injections during the extinction phase totally blocked the reinstatement of METH-induced CPP. Taken together, our results suggested a specific effect of histone acetylation on modulating distinct phases of METH-induced CPP and that treatment of NaB during the extinction phase not only produced beneficial effects on eliminating already established CPP but also blocked the reinstatement of METH-induced CPP. © 2016 Wiley Periodicals, Inc.

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“…after a drug‐primed reinstatement test), (2) where behavioural performance will be equivalent (level of responding is similar across groups on the final day of extinction) and (3) following a procedure that leads to a significant attenuation of subsequent reinstatement in NaB‐treated rats (Castino et al . ).…”

Section: Methodsmentioning

confidence: 97%

Persistent histone modifications at the BDNF and Cdk‐5 promoters following extinction of nicotine‐seeking in rats

Castino

Baker‐Andresen

Ratnu

et al. 2017

Genes Brain and Behavior

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Drugs of addiction lead to a wide range of epigenetic changes at the promoter regions of genes directly implicated in learning and memory processes. We have previously shown that the histone deactylase inhibitor, sodium butyrate (NaB), accelerates the extinction of nicotine-seeking and provides resistance to relapse. Here we explore the potential molecular mechanisms underlying this effect. Rats received intravenous nicotine or saline self-administration, followed by six days of extinction training, with each extinction session followed immediately by treatment with NaB or vehicle. On the last day of extinction, rats were sacrificed and the medial ventral prefrontal cortex retained for ChIP and qPCR. A history of nicotine exposure signficantly decreased H3K14 acetylation at the BDNF exon IV promoter, and this effect was abolished with NaB treatment. In contrats, nicotine self-administration alone, resulted in a significant decrease in histone methylation at the H3K27me3 and H3K9me2 marks in the promoter regions of BDNF exon IV and Cdk-5. Quantitative PCR identified changes in several genes associated with NaB treatment that were independent of nicotine exposure, however an interaction of nicotine history and NaB treatment was detected only in the expression of BDNF IV and BDNF IX. Together these results suggest that nicotine self-administration leads to a number of epigenetic changes at the BDNF promoter, and that these changes may contribute to the enhanced extinction of nicotine-seeking by NaB.

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Inhibition of Histone Deacetylases Facilitates Extinction and Attenuates Reinstatement of Nicotine Self-Administration in Rats

Cited by 29 publications

References 40 publications

Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats

Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats

Sodium butyrate modulates a methamphetamine‐induced conditioned place preference

Persistent histone modifications at the BDNF and Cdk‐5 promoters following extinction of nicotine‐seeking in rats

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