Systemic administration of anti-NGF antibodies to neonatal mice impairs 24-h retention of an inhibitory avoidance task while increasing ChAT immunoreactivity in the medial septum

Neonatal mice received subcutaneous injections of either antibody against murine NGF raised in goat (3 mg, injection volume 50 mu l) or preimmune serum on postnatal days 2, 4, 6, 8, 10, and 12. They were tested on postnatal days 15-16 or 20-21 for learning and 24-h retention of a passive avoidance step-through task. Immunostaining for choline acetyltransferase (ChAT) was measured in two cholinergic forebrain areas (septum and caudate-putamen) on postnatal day 16 or 21. Locomotor activity and exploratory behavior in an open-field test were also assessed on day 17 or 22, following a single administration of either scopolamine (2 mg/kg) or saline solution. While anti-NGF treatment did not affect acquisition on day 15, impairment in retention was evident on day 16. On days 20-21, no effects were found either on acquisition or on retention capabilities. Analysis of ChAT immunostaining revealed a significant increase of ChAT-immunopositive cells in the medial septal area in 16-day-old but not in 21-day-old mice. Behavior in the open-field test and age-typical response to scopolamine were not altered by anti-NGF at either of the two ages considered. These data support the view that immunological neutralization of endogenous NGF specifically affects the maturation of retention capabilities in altricial rodents, and confirm the involvement of forebrain cholinergic mechanisms in early memory processes.