Intrahippocampal Norleucine¹-Angiotensin IV mitigates scopolamine-induced spatial working memory deficits.
Depletion of cholinergic neurons in the hippocampus has been implicated in memory impairment and Alzheimer's Disease (AD). The brain angiotensin AT₄ receptor is co-localized with cholinergic neurons, and the AT₄ 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 AT₄ 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 Norleucine¹-Angiotensin IV (Nle¹-AngIV) significantly prevented the scopolamine-induced deficit. Consistent with previously published data on long-term spatial memory, our findings suggest that activation of AT₄ 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 Nle¹-AngIV-mediated cognitive improvement.
Olson
Mikel L
ML
Department of Psychology, Concordia College, 901 8th St. S., Moorhead, MN 56562, USA. molson@cord.edu
Cero
Ian J
IJ
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D009646:Norleucine / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism; D012601:Scopolamine / Q000633:toxicity*
C090830:AT4 receptor; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D009646:Norleucine; D012601:Scopolamine