Beneficial effect of chronic treatment with Org 2766 and alpha-MSH on impaired reversal learning of rats with bilateral lesions of the parafascicular area.

The effects of chronic treatment with the ACTH-(4-9) analogue Org 2766, alpha-MSH, and gamma 2-MSH were studied on T-maze reversal learning and on behavior assessed on the basis of open-field and other gross behavioral activities, grasping responses, inspection of various reflexes and electrical footshock sensitivity of rats with parafascicular lesions or sham-lesions. Repeated administration of Org 2766 and alpha-MSH to parafascicular area-lesioned rats resulted in functional recovery of impaired T-maze reversal learning. The structurally related neuropeptide gamma 2-MSH was without any effect. The alpha-MSH effect did not depend on time after lesioning as treatments during the first or second post-operative week were equally effective. Chronic peptide treatments did not change disturbed motor functions of parafascicular-lesioned rats, as measured by open-field activity, other gross behavioral activities and grasping responses. Since acute peptide treatments did not affect the impaired reversal learning performance of lesioned rats, the beneficial effect of Org 2766 and alpha-MSH could not be explained as a short-term effect on attention and motivation. It was more likely to be an accelerated recovery of cognitive function as a result of long-term neurotropic influences.