Numerous experimental and clinical studies have demonstrated that brain somatostatinergic neurotransmission plays an important role in the modulation of several brain functions, including learning and memory processes. Due to the gradual decline of cognitive performances occurring during aging, we evaluated whether an age-related modification of brain somatostatin gene activity occurred in discrete rat brain areas. Our study demonstrates that a significant reduction of pre-prosomatostatin mRNA levels occurred in aged animals (25 months) in the frontal cortex (-49%), in the parietal cortex (-80%) and in the striatum (-69%), despite the absence of changes in beta-actin gene expression. Conversely, no statistical differences were observed in the pre-prosomatostatin mRNA content of old animals in the hypothalamus. These results demonstrate that age-related alterations in somatostatin gene expression occur in the rat, and suggest that such alterations may be involved in the behavioral and cognitive impairments that occur during the aging process.