Novel Approaches in the Study of Brain Acetylcholine Function: Neuropharmacology, Neuroanatomy, and Behavior

Abstract

Over the last 30 years, it has become well-recognized that drugs blocking the muscarinic subtype of acetylcholine (ACh) receptors in the brain have selective and reproducible effects on behaviors requiring learning, memory, and stimulus discrimination in both animals (Hearst 1958; Carlton 1963; Warburton and Heise 1972; Bartus and Johnson 1976; Heise et al. 1976; Moore et al. 1976; Milar 1981; Spencer and Lal 1983; Spencer et al. 1985) and humans (Ostfeld and Aruguete 1962; Hrbek et al. 1971; Crow and Grove-White 1973; Drachman 1978; Mewaldt and Ghoneim 1979; Wesnes and Warburton 1984). Behavioral effects that are in many ways similar to those observed after central muscarinic blockade are also seen after electrolytic lesions of brain structures that involve a major cholinergic pathway, such as the medial-septal—hippocampal system (Douglas 1967; Walker et al. 1972; Myhrer 1975; Jarrard 1975, 1976; Johnson et al. 1977; Sinnamon et al. 1978), and after local infusions of muscarinic antagonists into the hippocampus (Leaton and Rech 1972; Ross and Grossman 1974; Leith and Barrett 1975; Ross et al. 1975; Blozovski 1979; Solomon and Gottfried 1981). Another major cholinergic projection passes from the nucleus basalis magnocellularis (nBM) to the neocortex, and lesions in this nucleus also produce antimuscarinic-like behavioral deficits (Flicker et al. 1983; Friedman et al. 1983), which are further increased by concurrent administration of centrally active muscarinic antagonists (Lo Conte et al. 1982).