Reward-related memory is an important factor in cocaine seeking. One necessary signaling mechanism for long-term memory formation is the activation of poly(ADP-ribose) polymerase-1 (PARP-1), via poly(ADP-ribosyl)ation. We demonstrate herein that auto-poly(ADP-ribosyl)ation of activated PARP-1 was significantly pronounced during retrieval of cocaine-associated contextual memory, in the central amygdala (CeA) of rats expressing cocaine-conditioned place preference (CPP). Intra-CeA pharmacological and short hairpin RNA depletion of PARP-1 activity during cocaine-associated memory retrieval abolished CPP. In contrast, PARP-1 inhibition after memory retrieval did not affect CPP reconsolidation process and subsequent retrievals. Chromatin immunoprecipitation sequencing revealed that PARP-1 binding in the CeA is highly enriched in genes involved in neuronal signaling. We identified among PARP targets in CeA a single gene, yet uncharacterized and encoding a putative transposase inhibitor, at which PARP-1 enrichment markedly increases during cocaine-associated memory retrieval and positively correlates with CPP. Our findings have important implications for understanding drug-related behaviors, and suggest possible future therapeutic targets for drug abuse.
|Number of pages||10|
|State||Published - 1 Apr 2017|
Bibliographical noteFunding Information:
ACKNOWLEDGMENTS This study was supported by NIH Grant No. 1 R21 DA027776-01 to GY and MCA. MS was supported by a grant from the Canadian Institute of Health Research (No. MOP-42411) and from the ERAnet FRSQ. EL and AF were each supported by a President's Doctoral Fellowship from Bar-Ilan University. EL was supported also by fellowships from the Israel Anti-Drug Authority and the Wolf Foundation, Israel, and the Richard and Edith Strauss Postdoctoral Fellowship in Medicine, McGill University. We thank IRCM for performing the Illumina sequencing. We thank Ori Yadid for graphical design of the brain sections. We thank Dr. Tamar Sadan for critical editing of the manuscript.