Effect of 5-aza-2-deoxycytidine microinjecting into hippocampus and prelimbic cortex on acquisition and retrieval of cocaine-induced place preference in C57BL/6 mice.
The long lasting addiction-related abnormal memory is one of the most important foundations for relapse. DNA methylation may be a possible mechanism for persistence of such memory. Here we injected the DNA methyltransferases (DNMTs) inhibitor, 5-aza-2-deoxycytidine (5-aza) into hippocampus CA1 area and prelimbic cortex during the stages of acquisition and expression of cocaine-induced place preference in C57BL/6 mice. Results showed that in CA1 DNA methylation inhibitors could restrain acquisition but had no impact on expression of the cocaine-induced conditioned place preference (CPP). On the contrary, in prelimbic cortex, 5-aza had no effect on acquisition but blocked expression. Our results indicated that DNA methylation in hippocampus is required for learning; while DNA methylation in prelimbic cortex is necessary for memory retrieval. The present finding is consistent with the role of the hippocampus as a structure contributing to cocaine-induced memory acquisition, and prelimbic cortex, a part of prefrontal cortex as an area responsible for cocaine-induced memory retrieval. In conclusion, DNA methylation does play an important role in drug-induced learning and memory although the detailed effect still calls for further research.
Han
Jin
J
Key lab of Mental Health, Institute of Psychology, Chinese Academy of Sciences Beijing, China.
Li
Yonghui
Y
Wang
Dongmei
D
Wei
Chuguang
C
Yang
Xiaoyan
X
Sui
Nan
N
D000818:Animals; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002404:Catheterization; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D019966:Substance-Related Disorders / Q000378:metabolism / Q000503:physiopathology
D004791:Enzyme Inhibitors; D000077209:Decitabine; D004248:DNA (Cytosine-5-)-Methyltransferases; D003042:Cocaine; D001374:Azacitidine