Takahiro Onodera1, Ritsuko Watanabe1, Kyi Kyi Tha1,
Yuka Hayashi2, Toshihiko Murayama1,#,
Yasunobu Okuma1, Chizuko Ono3, Yoneshiro Oketani3,
Masanori Hosokawa4 and Yasuyuki Nomura1,*
1Departmentﾊof Pharmacology, Graduate School of Pharmaceutical
Sciences, Hokkaido University, Sapporo 060-0812, Japan
2HokkaidoﾊFoundation for the Promotion of Scientific and Industrial
Technology, Sapporo 060-0001, Japan
3NewﾊDrug Development Research Center, Inc., Eniwa 061-1405,
Japan
4Departmentﾊof Senescence Biology, Chest Disease Research Institute,
Kyoto University, Kyoto 606-8397, Japan
#Presentﾊ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ﾊ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ﾊmonths
showed an increase of immobility in the test compared with SAMR1. Treatment
with desipramine (25ﾊmg/kg, i.p., 3ﾊ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
Copyrightｩ The Japanese Pharmacological Society 2000
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