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Depression-like behavior in the forced swimming test in PACAP-deficient mice: amelioration by the atypical antipsychotic risperidone

Authors :
Norihito Shintani
Mamoru Tanida
Masatoshi Takeda
Ryota Hashimoto
Xiaohong Guo
Michiyoshi Hatanaka
Katsuya Nagai
Hitoshi Hashimoto
Akemichi Baba
Akiko Yamamoto
Yoshiko Morita
Kazuhiro Tanaka
Source :
Journal of Neurochemistry. 110:595-602
Publication Year :
2009
Publisher :
Wiley, 2009.

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with pleiotropic functions. We report here that PACAP-deficient (PACAP-/-) mice showed increased immobility in a forced swimming test, which was reduced by the antidepressant desipramine, to a similar extent as in wild-type mice. The atypical antipsychotic risperidone and the selective serotonin (5-HT)(2) antagonist ritanserin normalized the depression-like behavior in PACAP-/- mice. The 5-HT(2) agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine-induced 5-HT syndrome was exaggerated in PACAP-/- mice, which suggests a 5-HT(2)-receptor-dependent mechanism in the depression-like behavior. The circadian rhythm of plasma corticosterone and body core temperature was significantly flattened in the mutants. mRNA expression of glucocorticoid receptor was reduced in the mutant hippocampus. The present results suggest that alterations in PACAP signaling might contribute to the pathogenesis of certain depressive conditions amenable to atypical antipsychotic drugs.

Details

ISSN :
14714159 and 00223042
Volume :
110
Database :
OpenAIRE
Journal :
Journal of Neurochemistry
Accession number :
edsair.doi.dedup.....72615e171cbe6c65823b3d48101e1bea
Full Text :
https://doi.org/10.1111/j.1471-4159.2009.06168.x