Because VIP is known to be neurotrophic in vitro, the present study tested whether peptide T (PT), an octapeptide with a pentapeptide sequence homologous to VIP, could prevent nucleus basalis (NBM)-induced degenerative changes in the parietal neocortex of aged rats. Aged (20-21 months old) Sprague-Dawley rats were given bilateral neurotoxic lesions of the NBM, and injected daily with PT (1 mg, IP) or vehicle solution for 5 months. Compared to unoperated controls, vehicle-treated NBM lesioned animals had: 1) a significant 17% decrease in overall cortical thickness, 2) significant decreases of 13-29% in the thickness of cortical layers II-IV, V, and VI, and 3) significant neuronal and glial cell loss in layer V. PT treatment prevented or attenuated these lesion-induced decreases in cortical thickness and attenuated the accompanying loss of large neurons in layer V. These results provide evidence that PT1 perhaps acting via VIP receptor stimulation, is neurotrophic and important for the integrity of brain tissue following denervation.