The effects of Org 2766 on the performance of sham, neocortical, and hippocampal-lesioned rats in a food search task.

The behavioral effects of an ACTH4-9 variant, Org 2766, given for one week postoperatively at a dose of 1 microgram/rat daily, were evaluated in animals given hippocampal, neocortical, or "sham" lesions. After the week during which the injections were given, the animals were tested for 5 days in a food-search task in which food was hidden in two recessed holes in the floor. On the next day the ability of the rats to find food in these same two baited holes was tested in the presence of 14 additional holes that were not baited. On the following day, the animals were tested again, this time with all 16 holes baited. To assess the long-term effects of Org 2766 treatment, the animals were tested once again 2-3 months later in the same apparatus with 16 empty holes. In general, rats with lesions restricted to the neocortex were severely impaired in the task and were unaffected by prior treatment with Org 2766. Animals with hippocampal damage quickly learned the task and were hyperactive. During the test session with 16 baited holes they showed differential behavioral changes suggesting attentional deficits not seen in "sham" operated rats. These deficits were attenuated by prior Org 2766 treatment, whereas the lesion-induced hyperactivity was not. Treatment with Org 2766 impaired all aspects of performance of "sham" operated animals.