Possible involvement of angiotensin-II and its receptors in experimental anterograde and retrograde amnesia

Abstract

Angiotensin-II is a multifunctional hormone that regulates blood pressure, plasma volume, neuronal functions, electrolyte balance, thrust and various other vital mechanisms. It acts through its receptors AT₁ and AT₂. The involvement of angiotensin-II and its receptors in cognition is still ambiguous. Therefore, the present study was designed to investigate the effect of angiotensin-II (2 μg/3 µl, i.c.v.), losartan (AT₁ blocker) (20 mg/kg, i.p.) and PD123177 (AT₂ blocker) (20 mg/kg, i.p.) on scopolamine (3 mg/kg, i.p), sodium nitrite (75 mg/kg, i.p.) and BN52021 (15 mg/kg, i.p.) induced amnesia in mice using water maze test. All the agents were administered 30 min prior to first acquisition trial for 4 consecutive days and on the 5th day during the retrieval trial. The study indicated that losartan significantly reversed the scopolamine and sodium nitrite induced anterograde amnesia. On the other hand losartan failed to produce any significant effect on sodium nitrite and BN52021 induced retrograde amnesia. Angiotensin-II and PD123177 did not exhibit any significant effect on scopolamine, sodium nitrite and BN52021 induced amnesia. The findings suggest that anterograde amnesia of scopolamine and sodium nitrite may be mediated through AT₁ receptor subtype only. These receptors are not involved in retrograde amnesia of sodium nitrite and BN52021. The finding also indicates that the brain structures involved in learning and memory are insensitive to exogenous angiotensin-II and PD123177 or have very less density of angiotensin receptors particularly AT₂ subtype.