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Reconsolidation of a cocaine associated memory requires DNA methyltransferase activity in the basolateral amygdala.
Sci Rep. 2015 Aug 20; 5:13327.SR

Abstract

Drug addiction is considered an aberrant form of learning, and drug-associated memories evoked by the presence of associated stimuli (drug context or drug-related cues) contribute to recurrent craving and reinstatement. Epigenetic changes mediated by DNA methyltransferase (DNMT) have been implicated in the reconsolidation of fear memory. Here, we investigated the role of DNMT activity in the reconsolidation of cocaine-associated memories. Rats were trained over 10 days to intravenously self-administer cocaine by nosepokes. Each injection was paired with a light/tone conditioned stimulus (CS). After acquisition of stable self-administration behaviour, rats underwent nosepoke extinction (10 d) followed by cue-induced reactivation and subsequent cue-induced and cocaine-priming + cue-induced reinstatement tests or subsequently tested to assess the strength of the cocaine-associated cue as a conditioned reinforcer to drive cocaine seeking behaviour. Bilateral intra-basolateral amygdala (BLA) infusion of the DNMT inhibitor5-azacytidine (5-AZA, 1 μg per side) immediately following reactivation decreased subsequent reinstatement induced by cues or cocaine priming as well as cue-maintained cocaine-seeking behaviour. In contrast, delayed intra-BLA infusion of 5-AZA 6 h after reactivation or 5-AZA infusion without reactivation had no effect on subsequent cue-induced reinstatement. These findings indicate that memory reconsolidation for a cocaine-paired stimulus depends critically on DNMT activity in the BLA.

Authors+Show Affiliations

Department of Pharmacy, Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China. Department of Biochemistry and Molecular Biology, Basic Medical College, Hebei Medical University, Shijiazhuang 050017, China.Department of Pharmacology, Medical College of Hunan Normal University, Changsha 410013, China.Department of Diagnosis Region of Function, Hebei Medical University Fourth Hospital, Hebei Medical University, Shijiazhuang, Hebei province, 050011.Department of Pharmacy, Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.Department of Pharmacy, Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.Department of Diagnosis Region of Function, Hebei Medical University Fourth Hospital, Hebei Medical University, Shijiazhuang, Hebei province, 050011.Department of Pharmacy, Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26289919

Citation

Shi, Hai-Shui, et al. "Reconsolidation of a Cocaine Associated Memory Requires DNA Methyltransferase Activity in the Basolateral Amygdala." Scientific Reports, vol. 5, 2015, p. 13327.
Shi HS, Luo YX, Yin X, et al. Reconsolidation of a cocaine associated memory requires DNA methyltransferase activity in the basolateral amygdala. Sci Rep. 2015;5:13327.
Shi, H. S., Luo, Y. X., Yin, X., Wu, H. H., Xue, G., Geng, X. H., & Hou, Y. N. (2015). Reconsolidation of a cocaine associated memory requires DNA methyltransferase activity in the basolateral amygdala. Scientific Reports, 5, 13327. https://doi.org/10.1038/srep13327
Shi HS, et al. Reconsolidation of a Cocaine Associated Memory Requires DNA Methyltransferase Activity in the Basolateral Amygdala. Sci Rep. 2015 Aug 20;5:13327. PubMed PMID: 26289919.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reconsolidation of a cocaine associated memory requires DNA methyltransferase activity in the basolateral amygdala. AU - Shi,Hai-Shui, AU - Luo,Yi-Xiao, AU - Yin,Xi, AU - Wu,Hong-Hai, AU - Xue,Gai, AU - Geng,Xu-Hong, AU - Hou,Yan-Ning, Y1 - 2015/08/20/ PY - 2015/03/12/received PY - 2015/07/22/accepted PY - 2015/8/21/entrez PY - 2015/8/21/pubmed PY - 2016/8/10/medline SP - 13327 EP - 13327 JF - Scientific reports JO - Sci Rep VL - 5 N2 - Drug addiction is considered an aberrant form of learning, and drug-associated memories evoked by the presence of associated stimuli (drug context or drug-related cues) contribute to recurrent craving and reinstatement. Epigenetic changes mediated by DNA methyltransferase (DNMT) have been implicated in the reconsolidation of fear memory. Here, we investigated the role of DNMT activity in the reconsolidation of cocaine-associated memories. Rats were trained over 10 days to intravenously self-administer cocaine by nosepokes. Each injection was paired with a light/tone conditioned stimulus (CS). After acquisition of stable self-administration behaviour, rats underwent nosepoke extinction (10 d) followed by cue-induced reactivation and subsequent cue-induced and cocaine-priming + cue-induced reinstatement tests or subsequently tested to assess the strength of the cocaine-associated cue as a conditioned reinforcer to drive cocaine seeking behaviour. Bilateral intra-basolateral amygdala (BLA) infusion of the DNMT inhibitor5-azacytidine (5-AZA, 1 μg per side) immediately following reactivation decreased subsequent reinstatement induced by cues or cocaine priming as well as cue-maintained cocaine-seeking behaviour. In contrast, delayed intra-BLA infusion of 5-AZA 6 h after reactivation or 5-AZA infusion without reactivation had no effect on subsequent cue-induced reinstatement. These findings indicate that memory reconsolidation for a cocaine-paired stimulus depends critically on DNMT activity in the BLA. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/26289919/Reconsolidation_of_a_cocaine_associated_memory_requires_DNA_methyltransferase_activity_in_the_basolateral_amygdala_ L2 - https://doi.org/10.1038/srep13327 DB - PRIME DP - Unbound Medicine ER -