Neurotransmitter Interactions and Responsivity to Cholinomimetic Agents

Abstract

There is now overwhelming evidence for the involvement of forebrain cholinergic systems in Alzheimer’s disease and the cognitive processes that subserve learning and memory (Perry et al., 1978; Bigl et al., 1987; Koshimura et al., 1987; Doucette et al., 1986; Ichimiya et al., 1986; Saper et al., 1985;Whitehouse, 1986; McGeer et al., 1984; Mann et al., 1986; Giacobini, 1990; Wenk et al., 1987). Support for the role of forebrain cholinergic systems in learning and memory can be gleaned from innumerable studies in which perturbation of forebrain cholinergic systems, whether through pharmacological means or lesion of the nucleus basalis of Meynert (nbM), has been demonstrated to profoundly impair learning and memory. This literature has been amply reviewed in recent articles and numerous chapters in this book (Wenk and Olton, 1987; Gold and Zornetzer, 1983; Dekker et al., 1991) and will not be reiterated here. In general, however, lesions of the nbM have been shown to impair performance on a very large variety of tasks and in a large and varied number of mammalian species. A smaller, but nevertheless voluminous, literature also attests to the ability of cholinomimetic agents such as physostigmine, oxotremorine, pilocarpine, etc. to at least partially reverse the learning and memory deficits induced by nbM lesions (Haroutunian et al., 1990c; Mandel et al., 1989; Fine et al., 1985; Bhat et al., 1990; Haroutunian et al., 1989b, 1990; Murray and Fibiger, 1985).