Muscarinic receptor antagonists in rats

The importance of cholinergic activity in the brain to learning and memory function was first recognized more than 30 years ago, when relatively low doses of certain muscarinic acetylcholine-receptor antagonists (e.g., the belladonna alkaloids atropine and scopolamine) were found to induce transient cognitive deficits in young human volunteers that resembled those observed in elderly (unmedicated) subjects.1 This work and a number of subsequent clinical studies indicated that antimuscarinics disrupt attention, ^2-4 the acquisition of new information, and the consolidation of memory.^1,4,5 Later studies found that scopolamine could alter certain features of the human electroencephalogram (e.g., delta, theta, alpha, and beta activity) in a fashion that mimics some of the changes observed in patients with Alzheimer’s disease (AD) (reviewed by Ebert and Kirch⁶).