The effect of continuous intraventricular infusion of L1 and NCAM antibodies on spatial learning in rats.

Recent studies suggest a role of the neural cell adhesion molecules L1 and NCAM in mechanisms of memory storage. In the present study we analyzed the effect of continuous intraventricular infusion of polyclonal antibodies directed against L1 (antiL1) or NCAM (antiNCAM) on the performance of male Wistar rats during the acquisition and retention of a spatial learning task (Morris water-maze). In this task animals have to learn the spatial position of a hidden escape platform in a water tank to escape onto it. During acquisition of the task animals with continuous infusion of antiNCAM - but not those infused with antiL1 - showed day-dependent attenuated learning in comparison to controls (P = 0.001). Control animals were either injected with vehicle (PBS) or with polyclonal antibodies raised against liver cell membrane. When the escape platform was removed during the retention test (transfer test), the performance of animals continuously infused with antiL1 as well as those continuously infused with antiNCAM showed an impaired search pattern when compared with the performance of control animals (P = 0.001 and 0.04, respectively). Whereas control animals spent up to 46% of their time searching for the platform in the correct quadrant, the time antiL1- and antiNCAM-infused animals spent in this quadrant was closer to chance level (30.5% and 36.5%), respectively). The present data provide additional support for an involvement of the two adhesion molecules L1 and NCAM in synaptic plasticity underlying memory storage.