Interactions between histaminergic and cholinergic systems in learning andmemory

The aim of this review is to survey biochemical, electrophysiological and b ehavioral evidence of the interactions between the cholinergic and histamin ergic systems and evaluate their possible involvement in cognitive processe s. The cholinergic system has long been implicated in cognition, and there is a plethora of data showing that cholinergic deficits parallel cognitive impairments in animal models and those accompanying neurodegenerative disea ses or normal aging in humans. Several other neurotransmitters, though, are clearly implicated in cognitive processes and interact with the cholinergi c system. The neuromodulatory effect that histamine exerts on acetylcholine release is complex and multifarious. There is clear evidence indicating th at histamine controls the release of central acetylcholine (ACh) locally in the cortex and amygdala, and activating cholinergic neurones in the nucleu s basalis magnocellularis (NBM) and the medial septal area-diagonal band th at project to the cortex and to the hippocampus, respectively. Extensive ex perimental evidence supports the involvement of histamine in learning and m emory and the procognitive effects of H-3 receptor antagonists. However, an y attempt to strictly correlate cholinergic/histaminergic interactions with behavioral outcomes without taking into account the contribution of other neurotransmitter systems is illegitimate. Our understanding of the role of histamine in learning and memory is still at its dawn, but progresses are b eing made to the point of suggesting potential treatment strategies that ma y produce beneficial effects on neurodegenerative disorders associated with impaired cholinergic function. (C) 2001 Elsevier Science B.V. All rights r eserved.