Comparative studies on the memory-enhancing actions of captopril and losartan in mice using inhibitory shock avoidance paradigm

Renin angiotensin system (RAS) in the central nervous system participates in the processing of sensory information, learning and memory processes. Inhibitors of RAS, particularly angiotensin converting enzyme (ACE) inhibitors and angiotensin II (Ang II) receptor antagonists are reported to have potential nootropic effects in various learning and memory paradigms. The neurochemical basis underlying nootropic effect of ACE inhibitors are unclear due to wide range of substrate for this enzyme. In this study, we compared the effect of ACE inhibitor captopril and a selective ATI receptor antagonist losartan in a step-up shock avoidance (active avoidance) task. Captopril (5-10 mg/kg) but not losartan (5-10 mg/kg) improved learning in the second trial of the acquisition test. However, both these drugs were equally effective in enhancing retention of memory when administered prior to training. Retention enhancing effect of captopril and losartan were reversed by post-acquisition test administration of L-NAME (15 mg/kg), dizocilpine (0.05 mg/kg) and scopolamine (0.1 mg/kg). On the basis of above observations, it is concluded that decrease in endogenous Ang II activity in the brain might result in improved cognitive performance by enhancing cGMP pathways. However facilitation of acquisition only by captopril may be due to other putative mechanisms. (C) 2001 Harcourt Publishers Ltd.