Key result
ACE inhibitors and ARBs reverse age- and scopolamine-induced memory deficits in preclinical models.
Why the study?
The cognitive enhancing properties of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were investigated in animal models of aging and chemically induced cognitive impairment.
Do ACE inhibitors and ARBs improve learning and memory in rat models of aging and scopolamine-induced amnesia?
Do ACE inhibitors and ARBs improve learning and memory in rat models of aging and scopolamine-induced amnesia?
ACE inhibitors and ARBs demonstrate cognitive enhancing effects in rat models of amnesia, potentially mediated by AChE inhibition and antioxidant regulation.
May enhance cognition in rat models; leaves open translation to human cognitive outcomes.
OBJECTIVE: The present study was designed to investigate cognitive enhancing property of angiotensin-converting enzymes inhibitors (ACEI) and angiotensin receptor blockers (ARBs) in rats. MATERIALS AND METHODS: The elevated plus maze (EPM), passive avoidance test (PAT), and water maze test (WMT) were used to assess cognitive enhancing activity in young and aged rats. Ramipril (10 mg/kg, p.o.), perindopril (10 mg/kg, i.p), losartan (20 mg/kg, i.p), and valsartan (20 mg/kg, p.o) were administered to assess their effect on learning and memory. Scopolamine (1 mg/kg, i.p) was used to impair cognitive function. Piracetam (200 mg/kg, i.p) was used as reference drug. RESULTS: All the treatments significantly attenuated amnesia induced by aging and scopolamine. In EPM, aged and scopolamine-treated rats showed an increase in transfer latency (TL) whereas, ACEI and ARBs showed a significant decrease in TL. Treatment with ACEI and ARBs significantly increased step down latencies and decreased latency to reach the platform in target quadrant in young, aged and scopolamine-treated animals in PAT and WMT, respectively. The treatments inhibited acetylcholinesterase (AChE) enzyme in the brain. Similarly, all the treatments attenuated scopolamine-induced lipid peroxidation and normalize antioxidant enzymes. CONCLUSION: The results suggest that the cognitive enhancing effect of ACEI and ARBs may be due to inhibition of AChE or by regulation of antioxidant system or increase in formation of angiotensin IV.
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Nade et al. (2015) studied Amnesia induced by aging and scopolamine. ACE inhibitors (ramipril, perindopril) and ARBs (losartan, valsartan) vs. Scopolamine-treated and aged controls; Piracetam as reference was evaluated on Cognitive enhancing activity assessed by elevated plus maze, passive avoidance test, and water maze test. ACE inhibitors and ARBs significantly attenuated amnesia induced by aging and scopolamine in rats, improving learning and memory metrics across multiple behavioral tests.
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