Pretraining Prevents Spatial Learning Impairment after Saturation

Spatial learning is impaired by NMDA receptor antagonists at doses that block hippocampal long-term potentiation (LTP). The deficit is not observed in animals that have received spatial or nonspatial pretraining in a different water maze. To determine whether this conditional impairment reflects debilitating senso-rimotor effects of NMDA receptor antagonists in naı̈ve animals, we compared spatial learning in naı̈ve and pretrained animals in which induction of LTP was blocked by a saturation procedure with no obvious effects on sensorimotor functions. Rats with unilateral hippocampal lesions were implanted with multiple bipolar stimulation electrodes in the angular bundle and a recording electrode in the dentate gyrus of the intact hemi-sphere. Half of the rats were pretrained to find a hidden plat-form in a water maze. A week later, pretrained and naı̈ve rats received either high-frequency (HF) or low-frequency (LF) stim