Preclinical research into cognition enhancers

Department of Psychology, University of Michigan, 4032 East Hall, 530 Church Street, Ann Arbor, MI 48109-1043, USA.
Trends in Pharmacological Sciences (Impact Factor: 11.54). 12/2006; 27(11):602-8. DOI: 10.1016/
Source: PubMed


The preclinical development of drugs to treat the cognitive symptoms of neuropsychiatric and neurological disorders is a formidable challenge. Evidence from a wide range of preclinical behavioral and neuropharmacological tests has formed the basis for predicting drug-induced cognition enhancement in normal volunteers and in patients with cognitive impairments. However, the limited validity of preclinical predictions of this enhancement in humans indicates that conventional screening for "broadly active" compounds represents a below-optimal research strategy. This article conceptualizes the evidence needed to improve the predictive validity of preclinical research designed to discover and characterize cognition enhancers. We suggest that the investigation of reciprocal relationships among molecular, cellular, behavioral and cognitive processes modulated by candidate drugs represents the core of such research. By contrast, the usefulness of simple and high-throughput screening tests for the detection of cognition enhancers might be restricted to advanced drug-finding programs that are guided by evidence of the modulation of neurocognitive relationships by cognition enhancers and that are informed by iterative preclinical-clinical cross-validation of research approaches. We stress the need for basic biopsychological research approaches in preclinical programs to find and characterize drugs to treat cognitive disorders.

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    • "Most CED candidates are evaluated in preclinical models, sets where standardized behavioral outcomes are easily assessed. Although the translation of preclinical data in valid clinical outputs poses several limitations (see Sarter, 2006), animal models remain extremely valuable to identify CED neurobiology (Roesler, 2011). "
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    • "Increases in attentional effort are thought to be under the control of the " central executive " (Baddeley, 1986) and the anterior attention system (Posner, 1994; Posner and Dehaene, 1994), including frontal and parietal regions. Attentional effort is thought to engage top-down attentional control processes that are employed in order to carry out goal-directed behaviors (Sarter et al., 2006). The right MFG results in this study support the idea that this region is particularly sensitive to the attentional control demands of a given task and is engaged to a greater extent under more demanding conditions. "
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    • "Attentional functions and capacities are key variables of cognitive performance (Sarter et al, 2005, 2006), and as such have been extensively targeted for drug-induced cognition enhancement. Cholinergic activity is necessary for the performance of attention tasks (eg McGaughy et al, 1996; for review see Sarter et al, 2005, 2006). The development of enzyme-coated microelectrodes allowing for the amperometric monitoring of real-time acetylcholine (ACh) release has revealed that brief (on the scale of seconds) increases in cholinergic activity (henceforth termed 'transients') mediate the detection of cues in attentional contexts (Parikh et al, 2007). "
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