Intrahippocampal Norleucine 1-Angiotensin IV mitigates scopolamine-induced spatial working memory deficits

Abstract

Depletion of cholinergic neurons in the hippocampus has been implicated in memory impairment and Alzheimer's Disease (AD). The brain angiotensin AT 4 receptor is co-localized with cholinergic neurons, and the AT 4 receptor has also been implicated in cognitive processing. The current investigation used the spatial win-shift version of the radial arm maze to determine the involvement of AT 4 receptors in spatial working memory formation. We initially established that intrahippocampal scopolamine significantly impaired the spatial working memory performance of Sprague-Dawley rats in the radial arm maze. We also demonstrated that subsequent intrahippocampal infusions of Norleucine 1-Angiotensin IV (Nle 1-AngIV) significantly prevented the scopolamine-induced deficit. Consistent with previously published data on long-term spatial memory, our findings suggest that activation of AT 4 receptors can compensate for impaired spatial working memory resulting from compromised muscarinic acetylcholine receptor function. We further demonstrate that the hippocampus is a site of action for Nle 1-AngIV-mediated cognitive improvement.