A partial agonist at strychnine-insensitive glycine sites facilitates spatial learning in aged rats

1-Aminocyclopropanecarboxylic acid (ACPC) is a high affinity ligand at stry chnine-insensitive glycine sites of the N-methyl-D-aspartate (NMDA) channel s and exhibits partial agonist properties in both biochemical and electroph ysiological measures. While ACPC was reported active in animal models used to evaluate potential antidepressants and anxiolytics, its effects on learn ing and memory are unknown. In the present study we investigated the effect s of ACPC on spatial learning in the Morris water maze. On a schedule of 12 learning trials, one trial per day, mature male Wistar rats (3 months of a ge) rapidly acquired the task. Electroconvulsive shocks applied after each of the learning trials markedly inhibited the consolidation of spatial memo ry. Administration of either a muscarinic agonist, arecoline (1 mg/kg) or A CPC (250 or 400 mg/kg) 20 min before each of the learning trials did not af fect the acquisition of spatial learning. Aged (16 months old) male Wistar rats demonstrated difficulties in the acquisition of spatial learning task. In these subjects, ACPC administered 20 min before each of the learning tr ials at a dose of 400, but not 250 mg/kg, facilitated the acquisition of sp atial memory as indicated on trials 3-5. ACPC did nor, affect the strength of spatial memory as assessed at the end of conditioning, by measuring swim ming behavior of rats in the pool with platform removed. It is suggested th at ACPC may alleviate learning deficits observed in the elderly.