Reconsolidation of a cocaine associated memory requires DNA methyltransferase activity in the basolateral amygdala.
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.
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.
Hai-Shui
HS
Shi
Department of Pharmacology, Medical College of Hunan Normal University, Changsha 410013, China.
Yi-Xiao
YX
Luo
Department of Diagnosis Region of Function, Hebei Medical University Fourth Hospital, Hebei Medical University, Shijiazhuang, Hebei province, 050011.
Xi
X
Yin
Department of Pharmacy, Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.
Hong-Hai
HH
Wu
Department of Pharmacy, Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.
Gai
G
Xue
Department of Diagnosis Region of Function, Hebei Medical University Fourth Hospital, Hebei Medical University, Shijiazhuang, Hebei province, 050011.
Xu-Hong
XH
Geng
Department of Pharmacy, Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.
Yan-Ning
YN
Hou
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000201:enzymology*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology
D004248:DNA (Cytosine-5-)-Methyltransferases; D003042:Cocaine; D001374:Azacitidine