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• W313710754 abstract "The previous optimism about the efficacy of cholinomimetics for the treatment of age- and dementia-associated syndromes was based on the assumption that a neurotransmitter replacement strategy, similar to the successful treatment of the dopaminergic deficiency in Parkinson’s disease, would attenuate the behavioral consequences of loss of basal forebrain cholinergic neurons. This “cholinergic hypothesis’’ (e.g., Bartus et al., 1985) was derived mainly from correlative neuropathological evidence (Whitehouse et al., 1981; Bowen et al., 1976; Palmer et al., 1987; Procter et al., 1988), and from animal studies that used basal forebrain lesions as a neurological model or muscarinic blockade as a pharmacological model (Hagan and Morris, 1988) for the behavioral consequences of cholinergic cell loss (Smith, 1988). However, it has more recently become evident that: (1) in the absence of a specific cholinotoxin, the basal forebrain model is invalid in terms of revealing the consequences of disruption to the basal forebrain cholinergic system (Robbins et al., 1989a; Salter and Dudchenko, 1991); (2) muscarinic antagonism produces behavioral deficits that model only some of the symptoms of dementia but spare major aspects such as the failure to retrieve information from remote memory (e.g., Beatty et al., 1986); and (3) traditional cholinomimetic drugs do not appear to exhibit clinically useful effects (for review see Sarter et al., 1991a). Reviewing this literature, Fibiger (1991) concluded that the contribution of the cholinergic system to the cognitive decline in dementia is unsettled, and that “programs aimed at developing cholinergic pharmacotherapies for the cognitive deficits in AD are based more on faith than on established facts” (p. 223). Fibiger, as well as others (e.g., Whalley, 1989) predicts that successful therapies will become obvious only after we learn more about etiological processes." @default.
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• W313710754 date "1992-01-01" @default.
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• W313710754 title "Modulation of Frontal Cortical Acetylcholine Release by Benzodiazepine Receptor Ligands: Age-Dependent Effects and Behavioral Correlates" @default.
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• W313710754 doi "https://doi.org/10.1007/978-1-4615-3432-7_21" @default.
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