The corticotropin releasing hormone receptors (CRHR) and their endogenous ligands coordinate the human response to acute or chronic stressful stimuli. While the appropriate response to acute stressors (fight or flight) can be life-saving, chronic stress is almost always harmful. Prior work has shown that ageing increases the susceptibility to stress. We studied the question of whether antagonism of corticotropin releasing hormone receptor 1 can prevent can prevent stress-induced anxiety and memory loss in rats. We used R121919 and antalarmin as nonpeptide antagonists in an isolation-restraint stress paradigm for 3 months. Rats received either R121919 or antalarmin in food chow or only food chow. Untreated aged rats showed weight loss, elevated corticosterone levels and anxiety-related behaviors and loss of cortical synapses as expected. Both R121919 and antalarmin prevented the effects observed in the untreated rats. Our results suggest that antagonism of the CHR stress system can mitigate the advance of Alzheimer's-likedisease in this model and that CRH antagonists may be useful as medications to blunt the advance of Alzheimer's disease.