Milacemide treatment in mice enhances acquisition of a Morris-type water maze task.

The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor appears to be involved with processes of learning and memory. A neutral amino acid binding site is known to exist on the NMDA complex. Glycine binds with high affinity to this site and has been found to potentiate NMDA activity. 2-N-Pentylaminoacetamide HCl (milacemide) is a glycine agonist that has been found to enhance performance of rodents in passive and active avoidance tasks and has improved the performance of humans in several word retrieval tasks. We evaluated the effects of milacemide on the performance of male C57BL/6J mice in a complex spatial task, the Morris water maze. Because NMDA receptor activation appears involved in induction of long-term potentiation, it was hypothesized that milacemide administration would be involved in task acquisition. Therefore, mice were treated with either milacemide (10 mg/kg) or vehicle 1 h prior to training on each of 4 consecutive days. Results indicated that mice treated with milacemide learned the task significantly faster than controls over 4 days of training, as measured by mean distance (cm) to reach the goal platform. Therefore, agonism of the glycine site on the NMDA receptor appears to facilitate performance of learning in a spatial memory task.

Dissociation of hippocampal and striatal contributions to spatial navigation in the water maze.

Two experiments were conducted to compare the effects of fornix/fimbria and caudate-putamen lesions in Long-Evans hooded rats (Rattus norvegicus) trained on two water maze tasks that differed in the type of spatial localization required for optimum solution. In Experiment 1, the lesioned rats and surgical controls were trained on the standard place task in the water maze (Morris, 1981) and given two postacquisition tests (a platform removal probe and platform relocation test). In Experiment 2, rats with similar lesions and control rats were trained on a modified cue navigation task. Fornix/fimbria lesions impaired a late stage of place task acquisition but did not impair acquisition of the cue task. Caudate-putamen lesions resulted in a severe place acquisition impairment and a transient cue acquisition impairment, both of which were characterized by an initial tendency to swim near the wall of the pool. Post-hoc analyses of the direction and angles of departure from the start points suggested that rats with fornix/fimbria lesions used non-allocentric spatial strategies to solve the place task. These rats also demonstrated a significantly weakened spatial bias for the former training quadrant on the platform removal probe and reduced flexibility in navigating to a novel platform location on the platform relocation test. In contrast, rats with caudate-putamen lesions showed a significant spatial bias for the former training quadrant but failed to cross the exact location within the quadrant where the platform was formerly positioned. The results suggest that the hippocampus mediates the allocentric spatial component of the water maze place task while the dorsomedial striatum may play an important role in the acquisition of the procedural aspects of both place and cue versions of the task.

Circadian phase-shifted rats show normal acquisition but impaired long-term retention of place information in the water task.

It is thought that circadian rhythms may influence learning and memory processes. However, research supporting this view does not dissociate a mnemonic impairment from other performance deficits. Furthermore, published reports do not specify the type of memory system influenced by the circadian system. The present study assessed the effects of phase shifting on acquisition and expression of place navigation in the water maze, a task sensitive to hippocampal dysfunction. The results showed that phase-shifting circadian rhythms in rats impaired the expression of place information on a retention test but not initial acquisition or encoding of place information. These results suggest that disruption of circadian rhythms may impair consolidation of previously encoded hippocampal place information.