title: Depression-like behavior in the forced swimming test in PACAP-deficient mice: amelioration by the atypical antipsychotic risperidone.
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.
authors.affiliation: Osaka University, Suita, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Norihito
authors.initials: N
authors.lastname: Shintani
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Michiyoshi
authors.initials: M
authors.lastname: Hatanaka
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Guo
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Morita
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanida
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nagai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
authors.forename: Akemichi
authors.initials: A
authors.lastname: Baba
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use*; D013550:Swimming
chemical_list: D014150:Antipsychotic Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018967:Risperidone; D003345:Corticosterone