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 SAMPO10. 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-HT(1A) 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 SAMP10 in were similar to those in SAMR1. The present findings represent the first neurochemical evidence of an increase of D₂/D₃ and 5-HT(1A) receptors in SAMP10. SAMP10 may be a useful model of aging associated depressive behavior.