Age-related decrease in spontaneity observed in senescence-accelerated mice (SAMP10) and the involvement of the dopaminergic system in behavioral disorders

Abstract We studied age-related behavioral changes in senescence-accelerated P10/Ta mice (SAMP10) reared under specific pathogen-free (SPF) conditions. Unlike SAMP8/Ta (SAMP8), the SAMP10 did not exhibit low anxiety-like behavior in the plus-maze test and the impairment of the passive avoidance task of SAMP10 was milder than that of SAMP8. SAMP10 showed more age-related abnormal behavior than did SAMP8, such as a decrease in shock sensitivity, increases in the duration of immobility during the tail suspension and the forced swimming tests and a decrease in swimming speed in a water maze task. SAMP10 showed a significant decrease in dopamine content in the anterior cortex. Furthermore, the behavioral depression observed in SAMP10 was ameliorated by dopaminergic stimulants such as apomorphine and a sustained release formulation of thyrotropin-releasing hormone (TRH-SR), at doses having no significant effects on spontaneous motor activity. These findings suggest that the dopaminergic function may contribute to behavioral depression. The present results indicate that SAMP10 shows a greater age-related decrease in the responsiveness to averse or stressful stimuli than do the R1 and P8 strains, which suggests that SAMP10 may be a useful animal model of age-related behavioral depression or decrease in spontaneity.