Reduced caloric intake obtained through long-term dietary restriction has been found beneficial in some animal models of neurodegeneration. We report here that rats maintained under dietary restriction from the second to the eighth month of age are fully protected towards degeneration of GABAergic neurons in the hippocampus and the olfactory-entorhinal cortex caused by systemic administration of the convulsant toxin, kainic acid. However, in a different model of excitotoxic neurodegeneration, injection of ibotenic acid in the forebrain magnocellular basal nucleus, the decrease of a cholinergic marker in the target areas of the cortex was only partially protected by dietary restriction. Thus, in different experimental models neurodegeneration can be differentially rescued by dietary restriction. Analysis of alterations in the expression of relevant genes in different experimental conditions, could help in better understanding these differences.