Effects of chronic stress and angiotensin II type 1 receptor blockade on rats' performance in the five-choice serial...

Pinpointing the bidirectional relationship between psychiatric and cardiovascular disorders holds the potential to tailor therapy and apply concepts of personalized treatment. Recent findings from both basic and clinical studies indicate effectives of central Renin-Angiotensin System (RAS) blockade in treatment of neuropsychiatric disorders, including the negative effects of stress. Here, to further investigate the long-term utility and translational value of angiotensin II type 1 receptor blockade on stress-induced impairment of learning and memory, we used an advanced behavioral paradigm - the five-choice serial reaction time task (5-CSRTT). Male Wistar rats, receiving vehicle (0.5 % metylcellulose) or telmisartan (TLM) (1 mg/kg), were subjected to a repeated restraint stress (21 days, 2.5 h/d) followed by training to the 5-CSRTT. Initial test parameters were altered on subsequent sessions according to individual animal's performance until reaching target parameters. Trained rats were subjected to a second 21-day trial of chronic stress and drug administration followed by the 5-CSRTT re-executed on target parameters. In the course of the study rats acquired accurate responses to the task at different rate. Unexpectedly, chronic stress preceding the 5-CSRTT training improved the procedural learning. Moreover, repeated restraint in previously trained subjects failed to alter the 5-CSRTT performance in statistically significant manner. Therefore, the translational value of animal model of chronic stress may be limited, as this commonly used research method failed to show long-lasting learning deficits. Our previous findings indicating 'anti-stress' capacity of TLM were not supported in the course of this study.