Takahiro Onodera1, Ritsuko Watanabe1, Kyi Kyi Tha1,
Yuka Hayashi2, Toshihiko Murayama1,#,
Yasunobu Okuma1, Chizuko Ono3, Yoneshiro Oketani3, Masanori Hosokawa4 and Yasuyuki Nomura1,*
1Department╩of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
2Hokkaido╩Foundation for the Promotion of Scientific and Industrial Technology, Sapporo 060-0001, Japan
3New╩Drug Development Research Center, Inc., Eniwa 061-1405, Japan
4Department╩of Senescence Biology, Chest Disease Research Institute, Kyoto University, Kyoto 606-8397, Japan
#Present╩address: Laboratory of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan
*To whom correspondence should be addressed.
Abstract: The senescence accelerated mouse (SAM) is known as a murine model of aging. SAM consists of senescence accelerated-prone mouse (SAMP) and senescence accelerated-resistant mouse (SAMR). Previous studies reported that SAMP10 exhibits age-related learning impairments and behavioral depression in a tail suspension test after 7╩months. We investigated the changes in emotional behavior in a forced swimming test and in receptors for dopamine and 5-hydroxytryptamine (5-HT) in SAMP10. SAMP10 at 8╩months showed an increase of immobility in the test compared with SAMR1. Treatment with desipramine (25╩mg/kg, i.p., 3╩days) in SAMP10 caused a decrease in immobility. In the cortex from SAMP10, [3H]quinpirole binding to D2/D3 dopamine receptors increased significantly compared with control SAMR1. In the hippocampus from SAMP10, [3H]8-hydroxy DPAT binding to 5-HT1A receptor increased. In midbrains from SAMP10, bindings of [3H]quinpirole and [3H]8-hydroxy DPAT increased. [3H]SCH23390 binding to D1/D5 receptors and [3H]ketanserin binding to 5-HT2 receptor in brain regions examined in SAMP10 were similar to those in SAMR1. The present findings represent the first neurochemical evidence of an increase of D2/D3 and 5-HT1A receptors in SAMP10. SAMP10 may be a useful model of aging associated depressive behavior.
Keywords: Senescence accelerated mouse, Depression, Dopamine, 5-Hydroxytryptamine, Receptor
Copyrightę The Japanese Pharmacological Society 2000
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