Increasing Dopamine and Acetylcholine Levels during Encoding Does Not Modulate Remember or Know Responses during Memory Retrieval in Healthy Aging—a Randomized Controlled Feasibility Study

Abstract

The retrieval of information from long-term memory can be associated with information regarding sources or context (recollection) or without further context (familiarity). The retrieval type depends on how information has been encoded previously, and this encoding process is supposed to be modulated by the neurotransmitters dopamine and acetylcholine. For example, acetylcholine levels in the hippocampus increase when one is confronted with novel information allowing for better encoding and, presumably, for retrieval of more detailed memories (recollection). On the other hand, a dopaminergic deficit such as in Parkinson’s disease has been shown to induce deficits in familiarity rather than in recollection-based retrieval. It is, however, unclear whether this finding arises from alterations in encoding, retrieval, or both. Moreover, other research has challenged this clear-cut dichotomy and linked dopamine to both familiarity and recollection, and acetylcholine to unspecific enhancement of memory for novel information. Thirty-nine healthy seniors (age range 62–77) participated in a remember/know task in which scenes that were presented with different repetition rates had to be encoded and retrieved on the following day. Neurotransmitter levels were modulated during encoding by administrating either levodopa (100 mg, N = 13) or galantamine (8 mg, N = 13) to one of two experimental groups. A third group received a placebo (N = 13). Across all groups, recognition memory increased as a function of stimulus repetition, and this effect was specifically pronounced for remember relative to know answers. Importantly, the drugs had no effect on recollection, familiarity, or overall recognition memory. The findings argue against a simple dichotomy of dopaminergic and cholinergic contributions to either recollection- or familiarity-based memory retrieval.