PARP-1 is required for retrieval of cocaine-associated memory by binding to the promoter of a novel gene encoding a putative transposase inhibitor.
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.
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.|Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
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Lax
The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan, Israel.
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Friedman
Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
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Massart
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
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Barnea
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
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Abraham
Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
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Cheishvili
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
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Zada
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
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Ahdoot
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
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Bareli
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
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Warhaftig
Department of Physiology and Pharmacology and Cardiac Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|The Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
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Visochek
Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.|Program for Epigenetics and Psychobiology, McGill University, Montreal, QC, Canada.|McGill Centre for Bioinformatics, McGill University, Montreal, QC, Canada.
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Suderman
Department of Physiology and Pharmacology and Cardiac Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|The Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
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Cohen-Armon
Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.|Program for Epigenetics and Psychobiology, McGill University, Montreal, QC, Canada.
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Szyf
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.|The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan, Israel.
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Yadid
D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D003042:Cocaine / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D019895:Transposases / Q000037:antagonists & inhibitors
C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D019895:Transposases; D020727:ADP-Ribosylation Factors; D003042:Cocaine