Involvement of the glutamatergic system in behavioral disorders in senescence-accelerated mice (SAMP8)

We previously reported that senescence-accelerated mice (SAMP8) showed age-related behavioral disorders such as learning and memory deficits and low anxiety-like behavior. To investigate the involvement of the brain glutamatergic system in the behavioral disorders observed in SAMP8, we examined the effects of MK-801, a non-competitive N-methyl-D-aspartic acid (NMDA) antagonist, on the behavior of a senescence-resistant control, SAMR1/TaSlc (SAMR1), and we tested the effects of D-cycloserine (DCS), a glycine site partial agonist, on behavioral disorders in SAMP8/ TaSlc (SAMP8). In the elevated plus-maze test, MK-801 significantly increased the number of entries into open arms and the time spent on open arms compared with the control group treated with saline. Furthermore, in the passive avoidance task, MK-801 caused dose-dependent decreases in avoidance latency in SAMR1. SAMP8 showed significant impairment in the acquisition of the passive avoidance response compared with SAMR1, even though they were trained repeatedly. DCS (3 or 10 mg/kg, intraperitoneally) tended to reduce the increased time spent on the open arms in SAMP8, and the administration of DCS (10 mg/kg, intraperitoneally) before each trial also tended to extend the avoidance latencies observed in SAMP8. These results indicate that the MK-801-induced behavioral disorders in SAMR1 are similar to those in SAMP8 and suggest that the glutamatergic system might be involved in the behavioral disorders observed in SAMP8. (C) 2003 Elsevier B.V. All rights reserved.