Comparative Effect of Lisinopril and Fosinopril in Mitigating Learning and Memory Deficit in Scopolamine-Induced Amnesic Rats.

Mohandas Rao,Veena Nayak,K L Bairy,Debasree Deb

doi:10.1155/2015/521718

Abstract

Lisinopril and fosinopril were compared on scopolamine-induced learning and memory deficits in rats. A total of eighty-four male Wistar rats were divided into seven groups. Group I received 2% gum acacia orally for 4 weeks, group II received normal saline, and group III received scopolamine (2 mg/kg/ip) as single dose. Groups IV and V received lisinopril ( 0.225 mg/kg and 0.45 mg/kg), while Groups VI and VII received fosinopril (0.90 mg/kg and 1.80 mg/kg), respectively, orally for four weeks, followed by scopolamine (2 mg/kg/ip) given 45 minutes prior to experimental procedure. Evaluation of learning and memory was assessed by using passive avoidance, Morris water maze, and elevated plus maze tests followed by analysis of hippocampal morphology and quantification of the number of surviving neurons. Scopolamine induced marked impairment of memory in behavioral tests which correlated with morphological changes in hippocampus. Pretreatment with fosinopril 1.80 mg/kg was found to significantly ameliorate the memory deficits and hippocampal degeneration induced by scopolamine. Fosinopril exhibits antiamnesic activity, indicating its possible role in preventing memory deficits seen in dementia though the precise mechanism underlying this effect needs to be further evaluated.

Highlights

Learning and memory are the most fundamental and closely related processes in the brain
Pretreatment with low and high doses of lisinopril and low dose of fosinopril did not show any significant difference in Transfer latency (TL) of rats on 1st and 2nd days compared to scopolamine group
Administration of scopolamine clearly produced memory deficits in rat performance in passive avoidance test as indicated by their shorter latency to enter into the dark compartment in the memory retention test compared to the control group

Summary

Introduction

Learning and memory are the most fundamental and closely related processes in the brain. Memory is defined as a change in mental representation caused by an experience, and learning is defined as a process of acquiring memory [1]. During this period of consolidation, memory can be disrupted with a wide variety of amnesia inducing agents. Scopolamine, a muscarinic receptor antagonist, induces memory deficits in rodents and healthy humans, and this effect has been proposed to mimic the cognitive and behavioral deficits seen during aging or in Alzheimer’s disease (AD) [2]. Scopolamine produces a reversible impairment in maintaining attention, processing of information, and the acquisition of new knowledge in both rodents [3] and humans [4]. The amnesic action produced by the administration of scopolamine has been widely used as an experimental model for the screening and validation of drugs with potential cognitive enhancing ability [5, 6]

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