Early postnatal treatment with ACTH(4-9) analog ORG 2766 improves adult spatial learning but does not affect behavioural stress reactivity

Studies on adult animals and humans have shown that the ACTH(4-9) analog OR G 2766 influences cognitive performance and possibly has neurotrophic effec ts. For this reason we studied the effect of ORG 2766 applied in early post natal life when brain structures and neuronal pathways are still developing . Our aim was to see whether such treatment during development would result in permanent changes in adult behavioural performance. Pups received subcu taneous injections of 1 mu g/g bodyweight ACTH(4-9) analog ORG 2766 on day 1, 3 and 5 after birth. Control animals in the same nest received saline in jections. When the animals had reached an adult age of 3 months they were s ubjected to a series of tests to measure their behavioural performance. In the first experiment, behavioural stress responses and anxiety were measure d by subjecting the rats to the following tests: open field, defensive bury ing, elevated plus maze, and conditioned fear teal. In a second experiment, adult cognitive function was measured in the Morris water-maze, a hippocam pus-related spatial learning test, and in the active avoidance test, a more amygdala-related nonspatial test. The results showed that animals treated with ORG 2766 during early postnatal life learned faster in the spatial Mor ris water-maze. The treatment had a positive effect on performance during t he acquisition phase of the learning task, while memory retrieval was not a ffected. Learning in the nonspatial active avoidance task did not change du e to the postnatal ACTH(4-9) treatment. In addition, there were no differen ces in the open field test, the defensive burying test, elevated plus maze and the conditioned fear test. The latter supports the conclusion that the differences in water-maze performance was due to a difference in learning s peed, rather than a difference in anxiety or behavioural stress reactivity. Analysis of [H-3]CORT binding capacity measured after the learning tests r evealed no differences in the hippocampal MR and GR concentration between n on-treated and treated animals. (C) 1999 Elsevier Science B.V. All rights r eserved.