Epigenetic modulation at the CCR2 gene correlates with the maintenance of behavioral sensitization to methamphetamine.
The intermittent administration of methamphetamine produces behavioral sensitization to methamphetamine. In the limbic forebrain, mainly including the nucleus accumbens, of mice that had been intermittently treated with methamphetamine, we found a significant increase in mRNA of a chemokine, CCR2. This increase was accompanied by a significant increase in histone H3 lysine 4 (H3K4) trimethylation at its promoter. Interestingly, the maintenance of sensitization to methamphetamine-induced hyperlocomotion was significantly decreased in CCR2 knockout mice. These findings suggest that increased CCR2 associated with epigenetic modification after the intermittent administration of methamphetamine may be associated with the maintenance of sensitization to methamphetamine-induced hyperlocomotion.
Ikegami
Daigo
D
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Narita
Minoru
M
Imai
Satoshi
S
Miyashita
Kazuhiko
K
Tamura
Rie
R
Narita
Michiko
M
Takagi
Shigemi
S
Yokomizo
Akiko
A
Takeshima
Hideyuki
H
Ando
Takayuki
T
Igarashi
Katsuhide
K
Kanno
Jun
J
Kuzumaki
Naoko
N
Ushijima
Toshikazu
T
Suzuki
Tsutomu
T
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000235:genetics*; D008032:Limbic System / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics*; D009714:Nucleus Accumbens / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D054390:Receptors, CCR2 / Q000235:genetics*
C515335:Ccr2 protein, mouse; D000697:Central Nervous System Stimulants; D012333:RNA, Messenger; D054390:Receptors, CCR2; D008694:Methamphetamine