Abstract
Background and Objective: Brain histamine and its receptors play a vital role in memory functions and also histamine H-3 receptor antagonist/inverse agonists have been proposed to treat cognitive disorders. This study examines the potential of clobenpropit, a selective antagonist on histamine H-3 receptors on Lipopolysaccharides(LPS)-induced cognitive impairment and neuronal cholinergic deficits in a mouse model. Materials and Methods: Consecutively 4 doses of LPS (250 mu g kg(-1), i.p.) were injected on days 22, 23, 24 and 25 of drug treatment in groups of mice to induce cognitive impairment. Clobenpropit (1 and 3 mg kg(-1), p.o.) was administrated continuously for 30 days and cognitive behaviours were assessed using Elevated Plus Maze (EPM), Novel Object Recognition (NOR) and Y-maze. Brain tissues were collected for the estimation of Acetylcholine (ACh) and Acetylcholinesterase (AChE) levels. Results: Clobenpropit reversed the behavioural deficits induced by LPS in behavioural models. Reduction of transfer latency in EPM test, higher exploration time with a novel object as well as improvement of discrimination index in NOR test and enhancement of novel arm performance, as well as the total number of both sessions entries in Y-maze test, were observed in LPS-induced mice. Besides, it reversed the LPS-induced cholinergic deficits in the brain by elevating the ACh levels and reducing AChE activities. Conclusion: Clobenpropit highlights to induce neuroprotection against LPS-induced cognitive impairments through facilitating cholinergic activity in mouse brain.