Postnatal intracerebroventricular administrations of NGF alter spatial memory in adulthood

The present work assessed the effects of intracerebroventricular injections (2 x 5 mg/2.5 mi) of recombined human nerve growth factor (rhNGF) at postn atal days 2 and 3 upon the development of spatial learning capacities in ra ts. The treated rats were trained at the age of 22 days to escape onto an i nvisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and reducing attention to the distant spatial cues. At the age of 2 months all the rats were retrained in the same task. Treatment effects were found in both immature and adult rats. The injectio n of NGF induced a slight alteration of the immature rats' performance. In contrast, a marked impairment of spatial abilities was shown in the 2-month -old rats. The most consistent effects were a significant increase in the e scape latency and a decrease bias towards the training platform area during probe trials. The reduction of spatial memory was particularly marked if t he subjects had been trained in a cued condition. Taken together, these exp eriments reveal that an acute pharmacological treatment that leads to trans ient modifications during early development might induce a behavioural chan ge long after treatment. Thus, the development and the maintenance of an ac curate spatial representation are tightly related to the development of bra in structures that could be altered by precocious NGF administrations. (C) 2000 Elsevier Science B.V. All rights reserved.