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 i n the processing of sensory information, learning and memory processes. Inh ibitors of RAS, particularly angiotensin converting enzyme (ACE) inhibitors and angiotensin II (Ang II) receptor antagonists are reported to have pote ntial nootropic effects in various learning and memory paradigms. The neuro chemical basis underlying nootropic effect of ACE inhibitors are unclear du e to wide range of substrate for this enzyme. In this study, we compared th e 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 t rial of the acquisition test. However, both these drugs were equally effect ive in enhancing retention of memory when administered prior to training. R etention enhancing effect of captopril and losartan were reversed by post-a cquisition test administration of L-NAME (15 mg/kg), dizocilpine (0.05 mg/k g) and scopolamine (0.1 mg/kg). On the basis of above observations, it is c oncluded that decrease in endogenous Ang II activity in the brain might res ult in improved cognitive performance by enhancing cGMP pathways. However f acilitation of acquisition only by captopril may be due to other putative m echanisms. (C) 2001 Harcourt Publishers Ltd.