Differential effect of ketamine on the reference and working memory versions of the Morris water maze task

The assumption that blockade of long-term potentiation by N-methyl-D-aspartate antagonists interferes with spatial memory was supported by experiments showing that 15 mg/kg ketamine impairs acquisition of navigation to a hidden platform but not to a visible platform. Higher doses were required to impair retrieval of overtrained place navigation. In a working memory version of the task, retrieval latencies were shorter than acquisition latencies with 4- to 15-min but not with 30- and 60-min delays. Latent learning was only effective with the 4-min delay. Ketamine prolonged the initial search of the hidden platform at 3 mg/kg and impaired latent learning but not active acquisition at 1.5-10 mg/kg. Comparison of behavioral and synaptic effects of ketamine suggests that long-term potentiation is a necessary condition, but not a sufficient condition, for acquisition of place navigation, because search strategy and latent place learning are impaired by ketamine doses not interfering with this synaptic phenomenon.