L-type voltage-dependent calcium channels facilitate acetylation of histone H3 through PKC[gamma] phosphorylation in mice with methamphetamine-induced place preference

• Published in: Journal of neurochemistry 2011-09, Vol.118 (6), p.1056
• Main Authors: Shibasaki, Masahiro, Mizuno, Koji, Kurokawa, Kazuhiro, Ohkuma, Seitaro
• Format: Article
• Language: English
• Subjects: Calcium; Methamphetamine; Phosphorylation; Rodents
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2011.07387.x

J. Neurochem. (2011) 118, 1056-1066. Abstract The present study investigated regulation of histone acetylation by L-type voltage-dependent calcium channels (VDCCs), one of the machineries to provide Ca2+ signals. Acetylation of histone through the phosphorylation of protein kinase Cγ (PKCγ) in the development of methamphetamine (METH)-induced place preference was demonstrated in the limbic forebrain predominantly but also in the nucleus accumbens of α1C subunit knockout mice. Chronic administration of METH produced a significant place preference in mice, which was dose-dependently inhibited by both chelerythrine (a PKC inhibitor) and nifedipine (an L-type VDCC blocker). Protein levels of acetylated histone H3 and p-PKCγ significantly increased in the limbic forebrain of mice showing METH-induced place preference, and it was also significantly attenuated by pre-treatment with chelerythrine or nifedipine. METH-induced place preference was also significantly attenuated by deletion of half the α1C gene, which is one of the subunits forming Ca2+ channels. Furthermore, increased acetylation of histone H3 was found in specific gene-promoter regions related to synaptic plasticity, such as Nrxn, Syp, Dlg4, Gria1, Grin2a, Grin2b, Camk2a, Creb, and cyclin-dependent kinase 5, in wild-type mice showing METH-induced place preference, while such enhancement of multiple synaptic plasticity genes was significantly attenuated by a deletion of half the α1C gene. These findings suggest that L-type VDCCs play an important role in the development of METH-induced place preference by facilitating acetylation of histone H3 in association with enhanced expression of synaptic plasticity genes via PKCγ phosphorylation following an increase in the intracellular Ca2+ concentration.