CREST in the nucleus accumbens core regulates cocaine conditioned place preference, cocaine-seeking behavior, and synaptic plasticity

Yasaman Alaghband, Enikö Kramár, Janine Kwapis, Earnest S. Kim, Thekla J. Hemstedt, Alberto J. López, André O. White, Amni Al-Kachak, Osasumwen V. Aimiuwu, Kasuni K. Bodinayake, Nicole C. Oparaugo, Joseph Han, K. Matthew Lattal, Marcelo A. Wood

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Epigenetic mechanisms result in persistent changes at the cellular level that can lead to long-lasting behavioral adaptations. Nucleosome remodeling is a major epigenetic mechanism that has not been well explored with regards to drug-seeking behaviors. Nucleosome remodeling is performed by multi-subunit complexes that interact with DNA or chromatin structure and possess an ATP-dependent enzyme to disrupt nucleosome-DNA contacts and ultimately regulate gene expression. Calcium responsive transactivator (CREST) is a transcriptional activator that interacts with enzymes involved in both histone acetylation and nucleosome remodeling. Here, we examined the effects of knocking down CREST in the nucleus accumbens (NAc) core on drug-seeking behavior and synaptic plasticity in male mice as well as drug-seeking in male rats. Knocking down CREST in the NAc core results in impaired cocaine-induced conditioned place preference (CPP) as well as theta-induced long-term potentiation in the NAc core. Further, similar to the CPP findings, using a self-administration procedure, we found that CREST knockdown in the NAc core of male rats had no effect on instrumental responding for cocaine itself on a first-order schedule, but did significantly attenuate responding on a second-order chain schedule, in which responding has a weaker association with cocaine. Together, these results suggest that CREST in the NAc core is required for cocaine-induced CPP, synaptic plasticity, as well as cocaine-seeking behavior.

Original languageEnglish (US)
Pages (from-to)9514-9526
Number of pages13
JournalJournal of Neuroscience
Volume38
Issue number44
DOIs
StatePublished - Oct 31 2018

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Neuronal Plasticity
Trans-Activators
Nucleus Accumbens
Cocaine
Nucleosomes
Calcium
Drug-Seeking Behavior
Epigenomics
Appointments and Schedules
Self Administration
Long-Term Potentiation
DNA
Enzymes
Acetylation
Histones
Chromatin
Adenosine Triphosphate
Gene Expression
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Alaghband, Yasaman ; Kramár, Enikö ; Kwapis, Janine ; Kim, Earnest S. ; Hemstedt, Thekla J. ; López, Alberto J. ; White, André O. ; Al-Kachak, Amni ; Aimiuwu, Osasumwen V. ; Bodinayake, Kasuni K. ; Oparaugo, Nicole C. ; Han, Joseph ; Lattal, K. Matthew ; Wood, Marcelo A. / CREST in the nucleus accumbens core regulates cocaine conditioned place preference, cocaine-seeking behavior, and synaptic plasticity. In: Journal of Neuroscience. 2018 ; Vol. 38, No. 44. pp. 9514-9526.
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title = "CREST in the nucleus accumbens core regulates cocaine conditioned place preference, cocaine-seeking behavior, and synaptic plasticity",
abstract = "Epigenetic mechanisms result in persistent changes at the cellular level that can lead to long-lasting behavioral adaptations. Nucleosome remodeling is a major epigenetic mechanism that has not been well explored with regards to drug-seeking behaviors. Nucleosome remodeling is performed by multi-subunit complexes that interact with DNA or chromatin structure and possess an ATP-dependent enzyme to disrupt nucleosome-DNA contacts and ultimately regulate gene expression. Calcium responsive transactivator (CREST) is a transcriptional activator that interacts with enzymes involved in both histone acetylation and nucleosome remodeling. Here, we examined the effects of knocking down CREST in the nucleus accumbens (NAc) core on drug-seeking behavior and synaptic plasticity in male mice as well as drug-seeking in male rats. Knocking down CREST in the NAc core results in impaired cocaine-induced conditioned place preference (CPP) as well as theta-induced long-term potentiation in the NAc core. Further, similar to the CPP findings, using a self-administration procedure, we found that CREST knockdown in the NAc core of male rats had no effect on instrumental responding for cocaine itself on a first-order schedule, but did significantly attenuate responding on a second-order chain schedule, in which responding has a weaker association with cocaine. Together, these results suggest that CREST in the NAc core is required for cocaine-induced CPP, synaptic plasticity, as well as cocaine-seeking behavior.",
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Alaghband, Y, Kramár, E, Kwapis, J, Kim, ES, Hemstedt, TJ, López, AJ, White, AO, Al-Kachak, A, Aimiuwu, OV, Bodinayake, KK, Oparaugo, NC, Han, J, Lattal, KM & Wood, MA 2018, 'CREST in the nucleus accumbens core regulates cocaine conditioned place preference, cocaine-seeking behavior, and synaptic plasticity', Journal of Neuroscience, vol. 38, no. 44, pp. 9514-9526. https://doi.org/10.1523/JNEUROSCI.2911-17.2018

CREST in the nucleus accumbens core regulates cocaine conditioned place preference, cocaine-seeking behavior, and synaptic plasticity. / Alaghband, Yasaman; Kramár, Enikö; Kwapis, Janine; Kim, Earnest S.; Hemstedt, Thekla J.; López, Alberto J.; White, André O.; Al-Kachak, Amni; Aimiuwu, Osasumwen V.; Bodinayake, Kasuni K.; Oparaugo, Nicole C.; Han, Joseph; Lattal, K. Matthew; Wood, Marcelo A.

In: Journal of Neuroscience, Vol. 38, No. 44, 31.10.2018, p. 9514-9526.

Research output: Contribution to journalArticle

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T1 - CREST in the nucleus accumbens core regulates cocaine conditioned place preference, cocaine-seeking behavior, and synaptic plasticity

AU - Alaghband, Yasaman

AU - Kramár, Enikö

AU - Kwapis, Janine

AU - Kim, Earnest S.

AU - Hemstedt, Thekla J.

AU - López, Alberto J.

AU - White, André O.

AU - Al-Kachak, Amni

AU - Aimiuwu, Osasumwen V.

AU - Bodinayake, Kasuni K.

AU - Oparaugo, Nicole C.

AU - Han, Joseph

AU - Lattal, K. Matthew

AU - Wood, Marcelo A.

PY - 2018/10/31

Y1 - 2018/10/31

N2 - Epigenetic mechanisms result in persistent changes at the cellular level that can lead to long-lasting behavioral adaptations. Nucleosome remodeling is a major epigenetic mechanism that has not been well explored with regards to drug-seeking behaviors. Nucleosome remodeling is performed by multi-subunit complexes that interact with DNA or chromatin structure and possess an ATP-dependent enzyme to disrupt nucleosome-DNA contacts and ultimately regulate gene expression. Calcium responsive transactivator (CREST) is a transcriptional activator that interacts with enzymes involved in both histone acetylation and nucleosome remodeling. Here, we examined the effects of knocking down CREST in the nucleus accumbens (NAc) core on drug-seeking behavior and synaptic plasticity in male mice as well as drug-seeking in male rats. Knocking down CREST in the NAc core results in impaired cocaine-induced conditioned place preference (CPP) as well as theta-induced long-term potentiation in the NAc core. Further, similar to the CPP findings, using a self-administration procedure, we found that CREST knockdown in the NAc core of male rats had no effect on instrumental responding for cocaine itself on a first-order schedule, but did significantly attenuate responding on a second-order chain schedule, in which responding has a weaker association with cocaine. Together, these results suggest that CREST in the NAc core is required for cocaine-induced CPP, synaptic plasticity, as well as cocaine-seeking behavior.

AB - Epigenetic mechanisms result in persistent changes at the cellular level that can lead to long-lasting behavioral adaptations. Nucleosome remodeling is a major epigenetic mechanism that has not been well explored with regards to drug-seeking behaviors. Nucleosome remodeling is performed by multi-subunit complexes that interact with DNA or chromatin structure and possess an ATP-dependent enzyme to disrupt nucleosome-DNA contacts and ultimately regulate gene expression. Calcium responsive transactivator (CREST) is a transcriptional activator that interacts with enzymes involved in both histone acetylation and nucleosome remodeling. Here, we examined the effects of knocking down CREST in the nucleus accumbens (NAc) core on drug-seeking behavior and synaptic plasticity in male mice as well as drug-seeking in male rats. Knocking down CREST in the NAc core results in impaired cocaine-induced conditioned place preference (CPP) as well as theta-induced long-term potentiation in the NAc core. Further, similar to the CPP findings, using a self-administration procedure, we found that CREST knockdown in the NAc core of male rats had no effect on instrumental responding for cocaine itself on a first-order schedule, but did significantly attenuate responding on a second-order chain schedule, in which responding has a weaker association with cocaine. Together, these results suggest that CREST in the NAc core is required for cocaine-induced CPP, synaptic plasticity, as well as cocaine-seeking behavior.

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