Depressive behavior and alterations in receptors for dopamine and 5-hydroxytryptamine in the brain of the senescence accelerated mouse (SAM)-P10.
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.
Onodera
T
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Watanabe
R
R
Tha
K K
KK
Hayashi
Y
Y
Murayama
T
T
Okuma
Y
Y
Ono
C
C
Oketani
Y
Y
Hosokawa
M
M
Nomura
Y
Y
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001552:Benzazepines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003863:Depression / Q000235:genetics / Q000378:metabolism*; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D051379:Mice; D019257:Quinpirole / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1
D001552:Benzazepines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D019257:Quinpirole; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin