Evidence from patients with Alzheimer's disease suggest that the basal forebrain cholinergic system plays an important role in memory. In support of this proposal, we have found impaired visual recognition memory in macaques with lesions to the major nuclei of this system. We have found further that recognition memory in normal monkeys can be improved by the cholinesterase inhibitor physostigmine and impaired by the cholinergic muscarinic-receptor blocker scopolamine. Another form of retention, spatial memory, has also been found to be impaired by scopolamine, although it is more resistant to such an effect than is recognition memory. In addition, our results indicate that scopolamine acts at a very early stage, suggesting an effect on primary, rather than secondary, memory. Finally, we have found that the scopolamine- induced impairment in recognition memory can be antagonized fully by physostigmine and partially by arginine vasopressin. Based on previous results indicating that THC may be exerting its effects through an action on the limbic system, we administered this drug to monkeys performing an interval-timing task known to be sensitive to hippocampal damage. Doses of THC that we previously found to impair visual recognition memory produced shifts in the monkeys interval-timing abilities that were in the same direction as those observed following hippocampal damage. In a series of experiments on habit formation, we administered the dopaminergic-neurotoxin MPTP to monkeys, producing learning and motor impairments that resolved within a few weeks. In spite of the recovery, the animals were more sensitive to the disruptive effects of scopolamine, suggesting residual damage to the dopaminergic system. Two years after the last dose of MPTP was given, substantial dopamine deficits were confirmed in these animals by positron emission tomography and biochemical analysis. At this time, the animals were impaired in learning a new task, detour reaching.
| Turchi, Janita; Saunders, Richard C; Mishkin, Mortimer (2005) Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys. Proc Natl Acad Sci U S A 102:2158-61 |
