Candesartan prevents impairment of recall caused by repeated stress in rats

Abstract

RationaleDeleterious effects of psychological stress on memory are increasingly important. Overexpression of the AT1 angiotensin receptors in brain has been found to participate in several negative effects of chronic stress including hypertension and a cognitive impairment.ObjectiveIn this study, we searched for the protective effects the AT1 angiotensin receptor blockade with candesartan against the adverse effects of repeated stress on recall of aversively and appetitively motivated behaviours in rats.MethodsTwo 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).ResultsStressed 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.ConclusionThese data strongly suggest that the AT1 angiotensin receptor blockade effectively counteracts deleterious effects of stress on recall of aversively and appetitively motivated memories in rats.

Angiotensin Type 1 Receptor Inhibition Enhances the Extinction of Fear Memory

“…However, at the doses we used, animals exposed to losartan for 2 weeks acquired fear similarly to control groups. These data are in line with other studies showing that losartan does not influence baseline anxiety levels in rodents when given acutely or chronically (48; 58; 59) or on acquisition of an aversive memory (60). Moreover, these data demonstrate that AT 1 receptor inhibition during fear conditioning enhances the extinction of an aversive memory and improves emotional learning, thus suggesting a role for endogenous angiotensin II in fear-related neurobiological processes.…”

Angiotensin II, a stress‐related neuropeptide in the CNS, facilitates micturition reflex in rats

“…However, the pharmacological targeting mechanism is not well clarified. Some AT 1 receptor antagonists (telmisartan and candesartan) were reported to be able to pass through the blood–brain barrier and were speculated to block AT 1 receptors in the brain (Gohlke et al ., ; Braszko et al ., ). A clinical study also showed that telmisartan has beneficial effects on cognitive and regional cerebral blood flow in elderly hypertensive patients with Alzheimer's disease (Kume et al ., ).…”

Angiotensin II AT1 receptor blockade by telmisartan reduces impairment of spatial maze performance induced by both acute and chronic stress

“…33 No such data are available for the RAM and BM. According to inverted-U-shaped fashion, suggesting that an optimal level of corticosterone will enhance memory and higher levels may impair it, 26 telmisartan treatment presumably diminish excessive release of corticosterone in stressed subjects, suppressing over-activation of the HPA axis and enhanced corticotrophin-releasing hormone, as has been recently described by Braszko et al 8 Noteworthy, time latencies in the MWM seems to efface among the stressed and non-stressed subjects on the second and the third day of testing. It is possible that control rats sooner than stressed rats switch from spatial to non-spatial strategies with overtraining.…”

“…7 However, this effect might be reduced by suppression of the brain RAS system, as we have previously shown using highly selective angiotensin type one (AT 1 ) receptor blockade, which effectively prevented deleterious effects of chronic stress on retrieval of memory in rats. 8,9 In this study, we attempted to evaluate the effect of AT 1 receptor blockade using telmisartan in hippocampaldependent memory tasks. Spatial and non-spatial cognition are two important aspects of cognitive function.…”