Hallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Senescence-Accelerated Mice

• NIIMI Kimie

  Brain Science and Life Technology Research Foundation Research Resources Center, RIKEN Brain Science Institute

• TAKAHASHI Eiki

  Research Resources Center, RIKEN Brain Science Institute

• ITAKURA Chitoshi

  Research Resources Center, RIKEN Brain Science Institute

Abstract

Many neuropharmacological agents modulate the activity and conformation of heptahelical G protein-coupled receptors and activate ligand-specific signaling pathways. The hallucinogenic chemical 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI), a serotonin receptor 2A (5-HT2AR) agonist, evokes extracellular signal-regulated kinase 1/2 (ERK1/2) signaling and head-twitch behavior. We previously reported that the senescence accelerated-prone mouse 6 (SAMP6) exhibited altered emotional behavior and increased levels of a serotonin-biosynthesizing enzyme compared to the senescence accelerated-resistant mouse 1 (SAMR1); however, the mechanism underlying the relationship between specific receptor signaling and behavioral phenotypes was unclear. In this study, we performed head-twitch tests and examined the total and phosphorylated levels of ERK1/2 and cAMP-responsive element-binding protein (CREB) in the bilateral somatosensory cortex to assess the differences between SAMP6 and SAMR1 using DOI. Although DOI dose-dependently increased the head-twitch response in both strains, the responses of SAMP6 given 0.3 and 1.0?mg/kg DOI were significantly greater than those of SAMR1 given DOI at the same doses. Although no dose-dependent increase in total ERK1/2 and total CREB expression was detected in response to DOI, the levels of phospho-ERK1/2 and -CREB increased in both strains. The phospho-ERK1/2 and -CREB levels in SAMP6 given 0.3 and 1.0?mg/kg DOI were significantly higher than those in SAMR1 given DOI at the same doses. These results indicate that SAMP6 increases DOI-dependent ERK1/2-CREB signaling leading to more head-twitch responses than SAMR1, and that SAMP6 could provide a useful model for examining the relationship between 5-HT2AR regulatory signaling and behavioral phenotypes.<br>

Journal

• Experimental Animals

  Experimental Animals 59 (4), 441-447, 2010

  Japanese Association for Laboratory Animal Science

Keywords

• DOI
• SAM
• Signaling pathway

Details

• CRID: 1390001205045419008
• NII Article ID: 130000298604
• NII Book ID: AA11032321
• DOI: 10.1538/expanim.59.441
• COI: 1:CAS:528:DC%2BC3cXhtF2qsbfK
• ISSN: 18817122
• ISSN: 00075124
• ISSN: 13411357
• NDL BIB ID: 10810687
• PubMed: 20660990
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10810687
• Web Site: http://www.jstage.jst.go.jp/article/expanim/59/4/59_4_441/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2011052931
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed