RGD Reference Report - BRG1 in the Nucleus Accumbens Regulates Cocaine-Seeking Behavior. - Rat Genome Database

RGD Reference Report - BRG1 in the Nucleus Accumbens Regulates Cocaine-Seeking Behavior. - Rat Genome Database

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BRG1 in the Nucleus Accumbens Regulates Cocaine-Seeking Behavior.
Authors:	Wang, Zi-Jun Martin, Jennifer A Mueller, Lauren E Caccamise, Aaron Werner, Craig T Neve, Rachael L Gancarz, Amy M Li, Jun-Xu Dietz, David M
Citation:	Wang ZJ, etal., Biol Psychiatry. 2016 Nov 1;80(9):652-660. doi: 10.1016/j.biopsych.2016.04.020. Epub 2016 May 6.
RGD ID:	597830063
Pubmed:	PMID:27422367 (View Abstract at PubMed)
PMCID:	PMC5050080 (View Article at PubMed Central)
DOI:	DOI:10.1016/j.biopsych.2016.04.020 (Journal Full-text)
BACKGROUND: Drug addiction is defined as a chronic disease characterized by compulsive drug seeking and episodes of relapse despite prolonged periods of drug abstinence. Neurobiological adaptations, including transcriptional and epigenetic alterations in the nucleus accumbens, are thought to contribute to this life-long disease state. We previously demonstrated that the transcription factor SMAD3 is increased after 7 days of withdrawal from cocaine self-administration. However, it is still unknown which additional factors participate in the process of chromatin remodeling and facilitate the binding of SMAD3 to promoter regions of target genes. Here, we examined the possible interaction of BRG1-also known as SMARCA4, an adenosine triphosphatase-containing chromatin remodeler-and SMAD3 in response to cocaine exposure. METHODS: The expression of BRG1, as well as its binding to SMAD3 and target gene promoter regions, was evaluated in the nucleus accumbens and dorsal striatum of rats using western blotting, co-immunoprecipitation, and chromatin immunoprecipitation following abstinence from cocaine self-administration. Rats were assessed for cocaine-seeking behaviors after either intra-accumbal injections of the BRG1 inhibitor PFI3 or viral-mediated overexpression of BRG1. RESULTS: After withdrawal from cocaine self-administration, BRG1 expression and complex formation with SMAD3 are increased in the nucleus accumbens, resulting in increased binding of BRG1 to the promoter regions of Ctnnb1, Mef2d, and Dbn1. Intra-accumbal infusion of PFI3 attenuated, whereas viral overexpression of Brg1 enhanced, cocaine-reinstatement behavior. CONCLUSIONS: BRG1 is a key mediator of the SMAD3-dependent regulation of cellular and behavioral plasticity that mediates cocaine seeking after a period of withdrawal.

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
SMAD3	Human	cocaine dependence	ameliorates	ISO	Smad3 (Rattus norvegicus)		RGD
SMARCA4	Human	cocaine dependence	ameliorates	ISO	Smarca4 (Rattus norvegicus)		RGD
Smad3	Rat	cocaine dependence	ameliorates	IMP			RGD
Smad3	Mouse	cocaine dependence	ameliorates	ISO	Smad3 (Rattus norvegicus)		RGD
Smarca4	Rat	cocaine dependence	ameliorates	IMP			RGD
Smarca4	Mouse	cocaine dependence	ameliorates	ISO	Smarca4 (Rattus norvegicus)		RGD

Genes (Rattus norvegicus)


Smad3 (SMAD family member 3)	Smarca4 (SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4)

Genes (Mus musculus)


Smad3 (SMAD family member 3)	Smarca4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4)

Genes (Homo sapiens)


SMAD3 (SMAD family member 3)	SMARCA4 (SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4)