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 a ccelerated-resistant mouse (SAMR). Previous studies reported that SAMP10 ex hibits age-related learning impairments and behavioral depression in a tail suspension test after 7 months. We investigated the changes in emotional b ehavior in a forced swimming test and in receptors for dopamine and 5-hydro xytryptamine (5-HT) in SAMP10. SAMP10 at 8 months showed an increase of imm obility 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, [H-3]quinpirole binding to D-2/D-3 dopamine receptors increase d significantly compared with control SAMR1. In the hippocampus from SAMP10 , [H-3]8-hydroxy DPAT binding to 5-HT1A receptor increased. In midbrains fr om SAMP10, bindings of [H-3]quinpirole and [H-3]8-hydroxy DPAT increased. [ H-3]SCH23390 binding to D-1/D-5 receptors and [H-3]ketanserin binding to 5- HT2 receptor in brain regions examined in SAMP10 were similar to those in S AMR1. The present findings represent the first neurochemical evidence of an increase of D-2/D-3 and 5-HT1A receptors in SAMP10. SAMP10 may be a useful model of aging associated depressive behavior.