The present study was designed to evaluate the effect of palmatine on memory of Swiss young male albino mice. Palmatine (0.1, 0.5, 1?mg/kg, i.p.) and physostigmine (0.1?mg/kg, i.p.) per se were administered for 10 successive days to separate groups of mice. Effect of drugs on learning and memory of mice was evaluated using elevated plus maze and Morris water maze. Brain acetylcholinesterase activity was also estimated. Effect of palmatine on scopolamine- and diazepam-induced amnesia was also investigated. Palmatine (0.5 and 1?mg/kg) and physostigmine significantly improved learning and memory of mice, as indicated by decrease in transfer latency using elevated plus maze, and decrease in escape latency during training and increase in time spent in target quadrant during retrieval using Morris water maze. The drugs did not show any significant effect on locomotor activity of the mice. Memory-enhancing activity of palmatine (1?mg/kg) was comparable to physostigmine. Palmatine (1?mg/kg) significantly reversed scopolamine- and diazepam-induced amnesia in mice. Palmatine and physostigmine also significantly reduced brain acetylcholinesterase activity of mice. Thus, palmatine showed memory-enhancing activity in mice probably by inhibiting brain acetylcholinesterase activity, through involvement of GABA-benzodiazepine pathway, and due to its antioxidant activity. 1. Introduction Dementia, the commonest form (accounting for approximately 60% of all cases) of which is Alzheimer’s disease (AD), mainly affects older people and it is estimated that, by 2050, more than 115 million people will have dementia [1]. AD is a neurodegenerative disorder characterized by cognitive and memory deterioration, progressive impairment of activities of daily living, and a multiplicity of behavioural and psychological disturbances [2]. The primary causes of AD appear to be (i) decreased cholinergic activity; (ii) deposition of amyloid-beta peptides in the brain; (iii) oxidative stress. Acetylcholinesterase (AChE) plays a key role in the regulation of the cholinergic system and hence, inhibition of AChE has emerged as one of the most promising strategies for the treatment of AD. One of the major therapeutic strategies is to inhibit the AChE, and hence, to increase the acetylcholine level in the brain [3]. The imbalance between the generation of free radicals and antioxidants has also been claimed to be a cause of AD [4]. Palmatine is a quaternary protoberberine alkaloid. It is typically yellow in color and is an active constituent of a number of plants, such as Coptidis rhizoma [5],
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