Candesartan prevents impairment of recall caused by repeated stress in rats

RATIONALE: Deleterious effects of psychological stress on memory are increasingly important. Overexpression of the AT(1) angiotensin receptors in brain has been found to participate in several negative effects of chronic stress including hypertension and a cognitive impairment. OBJECTIVE: In this study, we searched for the protective effects the AT(1) angiotensin receptor blockade with candesartan against the adverse effects of repeated stress on recall of aversively and appetitively motivated behaviours in rats. METHODS: Two groups of male Wistar rats were repeatedly stressed by keeping them daily (2 h/21 days) in tight plastic tubes. The subjects of the group 1 received candesartan (0.1 mg/kg, orally) each day before the stressing procedure. The rats of the group 2 received vehicle. Another two groups of rats (3 and 4) receiving candesartan and vehicle, respectively, were appropriately handled but not stressed. Next day, after ending the repeated stress procedure, all rats were tested in two cognitive paradigms: inhibitory avoidance (IA) and object recognition (OR). RESULTS: Stressed animals displayed decreased recall of the IA behaviour (p < 0.01) and decreased OR (p < 0.05). These effects were not seen in the animals stressed and concomitantly treated with candesartan. The auxiliary tests designed to control for the possible unspecific contribution of motor (open field) and emotional (elevated “plus” maze) effects of the experimental procedures to results of the cognitive tests showed no such contribution. CONCLUSION: These data strongly suggest that the AT(1) angiotensin receptor blockade effectively counteracts deleterious effects of stress on recall of aversively and appetitively motivated memories in rats.