Author(s)

Yoshihisa Kitamura^1*, Hiromi Hayashi¹, Yuka Onoue¹, Keiko Kuwatsuka¹, Ayaka Miyake¹, Ikuko Miyazaki², Masato Asanuma², Toshiaki Sendo¹

¹Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
²Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

We have shown previously that chronic administration of adrenocorticotropic hormone (ACTH) causes a significant decrease in hippocampal cell proliferation and neurogenesis. This effect in rats treated chronically with ACTH was not influenced by the chronic administration of imipramine, but was reversed by coadministration of imipramine and lithium. The present study was undertaken to further characterize the mechanism underlying the effect of imipramine and lithium on hippocampal cell proliferation and neurogenesis, by investigating the effects of treatment on the expression of brain-derived neurotrophic factor (BDNF), total cyclic adenosine monophosphate response element-binding protein (CREB), and phosphorylated CREB (pCREB) of the CREB signaling system, as well as Wnt 3a and cyclin D1 of the Wnt signaling pathway in the hippocampus of saline- and ACTH-treated rats. ACTH treatment significantly decreased the expression of cyclin D1. Treatment with imipramine and lithium increased the expression of cyclin D1 in ACTH-treated rats. However, the expression of BDNF, CREB, pCREB, and Wnt 3a did not change in either saline-treated or ACTH-treated rats. These findings suggest that the antidepressant effect of imipramine and lithium in ACTH-treatment-resistant rats may be attributed, at least in part, to an enhancement of cyclin D1 expression.

Adrenocorticotropic Hormone, Imipramine, Lithium, Cyclin D1, Cell Proliferation

Kitamura, Y. , Hayashi, H. , Onoue, Y. , Kuwatsuka, K. , Miyake, A. , Miyazaki, I. , Asanuma, M. and Sendo, T. (2014) Effects of Imipramine and Lithium on the Expression of Hippocampal Wnt 3a and Cyclin D1 in ACTH-Treated Rats. Journal of Behavioral and Brain Science, 4, 483-490. doi: 10.4236/jbbs.2014.411048.