You have full text access to this OnlineOpen article

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

  1. Hitoshi Hashimoto1,2,
  2. Ryota Hashimoto2,3,4,†,
  3. Norihito Shintani1,†,
  4. Kazuhiro Tanaka1,†,
  5. Akiko Yamamoto1,†,
  6. Michiyoshi Hatanaka1,
  7. Xiaohong Guo1,
  8. Yoshiko Morita1,
  9. Mamoru Tanida5,
  10. Katsuya Nagai5,
  11. Masatoshi Takeda2,3,
  12. Akemichi Baba1

Article first published online: 15 MAY 2009

DOI: 10.1111/j.1471-4159.2009.06168.x

Issue

Journal of Neurochemistry

Journal of Neurochemistry

Volume 110, Issue 2, pages 595–602, July 2009

Additional Information

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

Author Information

  1. 1

    Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan

  2. 2

    The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

  3. 3

    Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

  4. 4

    Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan

  5. 5

    Institute for Protein Research, Osaka University, Suita, Osaka, Japan

  1. †

    HH, RH, NS, KT and AY contributed equally to this work.

*Address correspondence and reprint requests to Akemichi Baba, Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: baba@phs.osaka-u.ac.jp

  • †

    HH, RH, NS, KT and AY contributed equally to this work.

Publication History

  1. Issue published online: 25 JUN 2009
  2. Article first published online: 15 MAY 2009
  3. Received March 16, 2009; accepted April 28, 2009.

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (625K)

Keywords:

  • atypical antipsychotic risperidone;
  • depression;
  • hypothalamus–pituitary–adrenal axis;
  • pituitary adenylate cyclase-activating polypeptide-deficient mice;
  • schizophrenia;
  • serotonin receptor

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-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.

View Full Article with Supporting Information (HTML) Get PDF (625K)