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Animal Bioresource in Japan

.: Home > Animal Bioresource in Japan > 2010 > Volume 59 Number 4 > Kimie NIIMI1)2), Eiki TAKAHASHI2) and Chitoshi ITAKURA2)

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

Kimie NIIMI1)2), Eiki TAKAHASHI2) and Chitoshi ITAKURA2)
1) Brain Science and Life Technology Research Foundation 2) 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.

Keywords :
DOI, SAM, Signaling pathway

Date Deposited : 21 Jun 2011 14:30

Last Modified : 21 Jun 2011 14:30

Official URL:

Volume 59, Number 4, - 2010

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