Analysis of motor function and dopamine systems of SAMP6 mouse

The motor function of senescence-accelerated mouse prone 6 (SAMP6) was evaluated with a battery of behavioral tests: locomotor activity test, traction test, wire hanging test, and rotating rod test. SAMP6 exhibited increased locomotor activity compared with senescence-accelerated mouse resistant 1 (SAMR1). There was no difference between SAMP6 and SAMR1 in the traction and wire hanging tests. In the rotating rod test, shorter retention times at each day in the accelerating version of the test were observed in SAMP6 compared with SAMR1, indicating a motor coordination deficit of SAMP6. To understand the mechanism involved, we focused on the dopamine system. Measurement of dopamine and its metabolites with HPLC revealed that the concentrations of dopamine in nucleus accumbens (NAcs) and cerebellum and of one or more dopamine metabolites in all tissues assayed were significantly higher in SAMP6 compared with SAMR1. Increases of dopamine transporter and dopamine receptor 1 (D1) in striatum, of dopamine receptor 3 (D3) in NAc, and of D1 and D3 in cerebellum in SAMP6 were observed. These results indicate that increased dopamine concentration in NAc and increased expression of D1 in striatum are possible cause(s) of the increased locomotor activity of SAMP6, and that increased D3 expression in cerebellum contributes to the motor coordination deficit of SAMP6.