Abstract：
:Given that cocaine induces neuroadaptations through regulation of gene expression, we investigated whether chromatin remodeling at specific gene promoters may be a key mechanism. We show that cocaine induces specific histone modifications at different gene promoters in striatum, a major neural substrate for cocaine's behavioral effects. At the cFos promoter, H4 hyperacetylation is seen within 30 min of a single cocaine injection, whereas no histone modifications were seen with chronic cocaine, consistent with cocaine's ability to induce cFos acutely, but not chronically. In contrast, at the BDNF and Cdk5 promoters, genes that are induced by chronic, but not acute, cocaine, H3 hyperacetylation was observed with chronic cocaine only. DeltaFosB, a cocaine-induced transcription factor, appears to mediate this regulation of the Cdk5 gene. Furthermore, modulating histone deacetylase activity alters locomotor and rewarding responses to cocaine. Thus, chromatin remodeling is an important regulatory mechanism underlying cocaine-induced neural and behavioral plasticity.
journal_name
Neuronjournal_title
Neuronauthors
Kumar A,Choi KH,Renthal W,Tsankova NM,Theobald DE,Truong HT,Russo SJ,Laplant Q,Sasaki TS,Whistler KN,Neve RL,Self DW,Nestler EJdoi
10.1016/j.neuron.2005.09.023subject
Has Abstractpub_date
2005-10-20 00:00:00pages
303-14issue
2eissn
0896-6273issn
1097-4199pii
S0896-6273(05)00790-7journal_volume
48pub_type
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