J.P. Bruno, M. Sarter, H.M. Arnold, C.L. Nelson, and C. Porter

Departments of Psychology and Neuroscience, The Ohio State University, Columbus, OH 43210

  The basal forebrain cortical cholinergic system mediates attentional processes. Dysfunctions in cortical cholinergic transmission contribute to the impaired attentional processing that represents a core symptom of several neuropsychiatric disorders, including Alzheimer's dementia, schizophrenia, and drug addiction. The rich literature on cholinergic function and cognition has prompted numerous investigations on cholinomimetic drugs as potential cognition enhancers. Investigations into nicotinic receptor stimulation-mediated facilitation of cognitive function has generated inconsistent findings in both humans and animals but generally suggest that nicotine and nicotinic agonists facilitate certain aspects of cognition, particularly attentional functions, following chronic administration or in smokers. Several studies have pointed to the potential usefulness of nicotinic receptor agonists as a treatment for age-related cognitive disorders, including Alzheimer’s disease.

The neurochemical mechanisms mediating the beneficial cognitive effects of nicotine or nicotine receptor agonists are obviously diverse. In addition to the well-documented effects of such drugs on mesolimbic dopaminergic systems, several encouraging microdialysis studies demonstrated that the acute administration of nicotine enhances cortical acetylcholine (ACh) release. Our laboratory contends that the continued development of animal models to study the relationship between nicotinic receptor activity and cognition must systematically address several issues that have thus far received too little attention. These include: 1) the need to examine potential drug effects in behavioral tasks that isolate specific components of cognition and that are clearly sensitive to changes in cholinergic transmission, 2) anticipated differences between the neurobehavioral effects of acute vs chronic nicotine and nicotinic agonists, 3) interactions between the level of activity in the cholinergic system and the effectiveness of potential cognition enhancers and 4) potential differences between the effects of nicotine in aged or brain damaged animals vs young, intact adults.

Behavioral and neurochemical data that address each of the above issues will be presented.  Behaviorally, evidence in support of the beneficial attentional effects of nicotinic receptor ligands support the assumption that these effects are mediated critically via modulation of the activity of cortical cholinergic inputs.  Neurochemically, we will present data on the effects of nicotinic ligands on cortical ACh efflux using microdialysis techniques in awake rats.

The authors’ research was supported by NIH Grants NS32938, MH57436, NS37026 and AG10173. Session sponsored by the "Association pour la Recherche sur les Nicotianés", Paris, France.