@misc{oai:repo.qst.go.jp:00070923,
 author = {Maeda, Jun and Tokunaga, Masaki and Zhang, Ming-Rong and Minamihisamatsu, Takeharu and Fukumura, Toshimitsu and Miyakawa, Tsuyoshi and Suhara, Tetsuya and Higuchi, Makoto and 前田 純 and 徳永 正希 and 張 明栄 and 南久松 丈晴 and 福村 利光 and 宮川 剛 and 須原 哲也 and 樋口 真人},
 month = {Aug},
 note = {The alpha isoform of calcium/calmodulin-dependent protein kinase II (CaMKIIalpha) is the most important serine/threonine-specific protein kinase for the regulation of neural plasticity signaling downstream of excitatory amino acid receptors. Mice deficient in CaMKII manifest several serious emotional dysfunctions, such as lack of fear response and hyperaggression. These abnormal behaviors are presumably caused by dysregulated serotonergic neurotransmissions, but detailed molecular mechanisms are unclear. In the present study, binding of radioligands to serotonin 1A (5-HT1A) receptors in the brain of mice heterozygous for the null mutation (hKO) of CaMKIIalpha was analyzed by in vivo positron emission tomography (PET) and in vitro autoradiography in a comparative manner in order to clarify functional changes of the serotonergic system by the deficiency of CaMKIIalpha. In vitro autoradiography with [18F]MPPF and [3H]8-OH-DPAT demonstrated that density of 5-HT1A receptors in the hippocampus of CaMKIIhKO mice was reduced to one-third of that in wild-type mice. This observation was consistent with results of in vivo PET with [11C]WAY100635. However, in vivo PET also indicated no difference in hippocampal distribution volume ratio for [18F]MPPF between wild-type and CaMKIIalpha hKO mice. In addition, a significant increase of in vivo [18F]MPPF binding was found in the frontal cortex of CaMKIIalpha hKO mice, in contrast to no marked genotype-related changes of in vitro autoradiographic binding of this radioligand in the same brain region. Pretreatment of wild-type mice with fenfluramine induced a decrease of in vivo [18F]MPPF binding conceivably due to displacement of radioligands by overflowing serotonin, whereas no overt effects of fenfluramine were observed in the CaMKIIalpha hKO mouse brain. These results implicate decline in serotonergic transmissions via 5-HT1A receptors as a mechanism by which in vivo binding of [18F]MPPF in the CaMKIIalpha hKO brain was augmented relative to its in vitro binding., The 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM12)},
 title = {Altered serotonin release and serotonin 1A receptor density in CaMKIIalpha deficient mice assessed by a comparison of in vivo PET and in vitro autoradiographic data},
 year = {2012}
}