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Depression‐like behavior in the forced swimming test in PACAP‐deficient mice: amelioration by the atypical antipsychotic risperidone
Author(s) -
Hashimoto Hitoshi,
Hashimoto Ryota,
Shintani Norihito,
Tanaka Kazuhiro,
Yamamoto Akiko,
Hatanaka Michiyoshi,
Guo Xiaohong,
Morita Yoshiko,
Tanida Mamoru,
Nagai Katsuya,
Takeda Masatoshi,
Baba Akemichi
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06168.x
Subject(s) - endocrinology , ritanserin , medicine , behavioural despair test , desipramine , serotonin , agonist , corticosterone , atypical antipsychotic , 5 ht receptor , antagonist , serotonin reuptake inhibitor , hippocampus , receptor , antipsychotic , psychology , antidepressant , biology , hormone , schizophrenia (object oriented programming) , psychiatry
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.