Blockade of Central Cholinergic Receptors Impairs New Learning and Increases Proactive Interference in a Word Paired-Associate Memory Task

Experimental data and computational models suggest that blockade of muscarinic cholinergic receptors impairs paired-associate learning and increases proactive interference (E. DeRosa & M. E. Hasselmo, 2000; M. E. Hasselmo & J. M. Bower, 1993). The results presented here provide evidence in humans supporting these hypotheses. Young healthy subjects first learned baseline word pairs (A-B) and, after a delay, learned additional overlapping (A-C) and nonoverlapping (D-E) word pairs. As predicted, when compared with subjects who received the active placebo glycopyrrolate (4 μg/kg) and subjects who were not injected, those who received scopolamine (8 μg/kg) showed (a) overall impairment in new word paired-associate learning, but no impairment in cued recall of previously learned associates; and (b) greater impairment in learning overlapping (A-C) compared with nonoverlapping (D-E) paired associates.