Intrahippocampal blockade of nicotinic or muscarinic receptors fails to impair nonnavigational spatial memory in macaques.

Abstract

Cholinergic neurotransmission within the hippocampus has long been suggested to play a pivotal role in memory processing, based partly on the assumption that the well-established amnestic effects of systemic cholinergic receptor blockade are mediated by the hippocampus. However, experimental evidence suggests that this may not be the case; a growing number of studies employing selective lesion or pharmacological approaches to disrupt cholinergic transmission within the hippocampus have failed to find robust deficits in either learning or memory, primarily in rodent models. Here, we evaluated the contribution of nicotinic acetylcholine receptor (nAChR)- and muscarinic acetylcholine receptor (mAChR)-mediated neurotransmission in the hippocampus of rhesus macaques for performance in a hippocampal-dependent spatial memory task, the Hamilton Search Task. We infused the nAChR antagonist, mecamylamine, or the mAChR antagonist, scopolamine, and evaluated performance on a within-subject basis. Neither treatment impaired performance under any task conditions. These data demonstrate that the hippocampus is not the critical site for the mnemonic actions of cholinergic neurotransmission, at least in the context of spatial memory.