title: Calcitonin gene-related peptide pre-administration acts as a novel antidepressant in stressed mice.
abstract: Calcitonin gene-related peptide (CGRP) is a neuropeptide that has potent vasodilator properties and is involved in various behavioral disorders. The relationship between CGRP and depression-like behavior is unclear. In this study, we used chronically stressed mice to investigate whether CGRP is involved in depression-like behavior. Each mouse was exposed to restraint and water immersion stress for 15 days. After stress exposure, mice were assessed using behavioral tests: open field test, forced swim test and sucrose preference test. Serum corticosterone levels, hippocampal proliferation and mRNA expression of neurotrophins were measured. After stress exposure, mice exhibited depression-like behavior and decreased CGRP mRNA levels in the hippocampus. Although intracerebroventricular CGRP administration (0.5 nmol) did not alter depression-like behavior after 15-day stress exposure, a single CGRP administration into the brain, before the beginning of the 15-day stress exposure, normalized the behavioral dysfunctions and increased nerve growth factor (Ngf) mRNA levels in stressed mice. Furthermore, in the mouse E14 hippocampal cell line, CGRP treatment induced increased expression of Ngf mRNA. The NGF receptor inhibitor K252a inhibited CGRP's antidepressant-like effects in stressed mice. These results suggest that CGRP expression in the mouse hippocampus is associated with depression-like behavior and changes in Ngf mRNA levels.
authors.affiliation: Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Hashikawa-Hobara
authors.affiliation: Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Ogawa
authors.affiliation: Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsuo
authors.affiliation: Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Medicinal Drug Design, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Zamami
authors.affiliation: Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashikawa
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002460:Cell Line; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000378:metabolism; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide; D003345:Corticosterone