HH, RH, NS, KT and AY contributed equally to this work.
Depression-like behavior in the forced swimming test in PACAP-deficient mice: amelioration by the atypical antipsychotic risperidone
Article first published online: 15 MAY 2009
© 2009 The Authors. Journal Compilation © 2009 International Society for Neurochemistry
Journal of Neurochemistry
Volume 110, Issue 2, pages 595–602, July 2009
How to Cite
Hashimoto, H., Hashimoto, R., Shintani, N., Tanaka, K., Yamamoto, A., Hatanaka, M., Guo, X., Morita, Y., Tanida, M., Nagai, K., Takeda, M. and Baba, A. (2009), Depression-like behavior in the forced swimming test in PACAP-deficient mice: amelioration by the atypical antipsychotic risperidone. Journal of Neurochemistry, 110: 595–602. doi: 10.1111/j.1471-4159.2009.06168.x
- Issue published online: 25 JUN 2009
- Article first published online: 15 MAY 2009
- Received March 16, 2009; accepted April 28, 2009.
- atypical antipsychotic risperidone;
- hypothalamus–pituitary–adrenal axis;
- pituitary adenylate cyclase-activating polypeptide-deficient mice;
- serotonin receptor
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-HT2 agonist (±)-2,5-dimethoxy-4-iodoamphetamine-induced 5-HT syndrome was exaggerated in PACAP−/− mice, which suggests a 5-HT2-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.