Selective effects of nerve growth factor on spatial recent memory as assessed by a delayed nonmatching-to-position task in the water maze

Nerve growth factor (NGF) ameliorates age-related deficits in certain types of memory in rats. Although the effects of NGF on reference memory are well documented, the influence of NGF on recent memory is less well understood. The issue of recent memory is of primary importance in the design of therapies for cognitive disorders, because this type of memory is impaired in elderly humans and is severely affected early in the course of Alzheimer's disease (AD). The present study was designed to evaluate the effects of NGF on recent memory in a task that used escape from water as the motivating stimulus and used the same design as forced-choice recognition tasks given to humans. Fischer-344 rats, 4 months old (4MO) or 23 months old (23MO), were pretested in a new spatial recent memory task designed for the Morris water maze, a delayed nonmatching-to-position task, and infused intraventricularly with recombinant human NGF or vehicle. After 2 weeks of NGF infusion, no substantial changes in behavior were observed in either age group. However, NGF treatment extended over 4 weeks improved considerably the choice accuracy of 23MO rats to a level similar to the performance of 4MO rats. These results, together with our previous work (Markowska et al., 1994), indicate that the effects of NGF on spatial recent memory are more intense than on spatial reference memory. NGF suppressed the body weight gain in 4MO rats but did not affect 23MO rats. In 23MO rats, NGF mildly counteracted age-related deficits in inhibitory avoidance, but did not have an effect in young rats.