Arc (Activity-regulated cytoskeletal-associated protein) is a member of the immediate-early gene (IEG) family protein. Because of its critical role in learning and memory, it is widely considered to be an important protein in synaptic plasticity and related neurobiological functions. Alcoholic extract of Ashwagandha leaves (i-Extract) was recently shown to have preventive and therapeutic potential for scopolamine-induced amnesia and glutamate-induced excitotoxicity. In the present study, we investigated the involvement of Arc in scopolamine-induced amnesia and its recovery by i-Extract with particular focus to the changes in Arc expression in the hippocampus and cerebral cortex of mice. Morris water maze test showed that spatial learning and memory of mice were drastically reduced by scopolamine administration but improved with i-Extract treatment as compared to control and scopolamine-challenged mice. Molecular analysis revealed a remarkable decline in Arc expression in both hippocampus and cerebral cortex of amnesic mice, which was recovered after i-Extract treatment. Interestingly, Arc expression showed better recovery in the hippocampus than the cerebral cortex and the pre-treatment with i-Extract was more effective than the post-treatment. These findings suggest that Arc may be involved in i-Extract mediated recovery from amnesia. Copyright © 2013 Elsevier Inc. All rights reserved.