[Experimental techniques for developing new drugs acting on dementia (8)--Characteristics of behavioral disorders in senescence-accelerated mouse (SAMP8): possible animal model for dementia]

Abstract

Experimental methods to assess age-related behavioral disorders such as impairments of learning and memory, emotional disorder and abnormality of circadian rhythms in senescence-accelerated mice (SAMP8), and the characteristics of the behavioral disorders are described. SAMP8 shows age-related impairments of learning and memory assessed by passive avoidance, two-way active avoidance and Morris water maze tasks, and the impairments are significant even at 2 months of age and become obvious with aging. Age-related emotional disorder is also observed in SAMP8 mice. SAMP8 mice exhibit age-related emotional changes as compared with the SAMR1 control; they show apparent increases in the number of entries into open arms and time spent on open arms in the elevated plus-maze test. In addition, punished drinking in SAMP8 is markedly increased in the water-drinking conflict test. It is implicated that the reduced anxiety-like behavior is closely related to learning impairments in the strain. Cholinergic drugs and a sustained formulation of thyrotropin-releasing hormone ameliorate impairments of learning behavior and the emotional disorder in SAMP8. Furthermore, SAMP8 shows an age-dependent abnormality of circadian rhythms of spontaneous motor activity (SMA) and ingestive behavior compared with the SAMR1 control, diurnal SMA and water intake in SAMP8 being higher than those of SAMR1. These findings suggest that the SAMP8 strain is a useful animal model for learning and memory impairments, emotional disorder and abnormality of circadian rhythms in patients with dementia.