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Assessing a vigilance decrement in aged rats: effects of pre-feeding,task manipulation,and psychostimulants
Authors:Grottick Andrew J  Higgins Guy A
Affiliation:(1) PRBN-B, F. Hoffmann-La Roche AG, 4070 Basel, Switzerland,;(2) Arena Pharmaceuticals Inc., 6166 Nancy Ridge Drive, San Diego, CA 92121, USA,;(3) Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA,
Abstract:Abstract Rationale. In studies assessing sustained attention in humans, performance is often characterised by a decline in function over time. This response pattern, termed the vigilance decrement, is sensitive to manipulations affecting task difficulty, and to reversal with psychostimulant drugs. A valid test of attention in non-human species requires both comparable characteristics of performance, and sensitivity to similar psychoactive drugs. The five-choice serial reaction time task (5-CSRTT) has been described as a test of sustained attention in the rat, however, studies describing vigilance decrements and performance effects of psychostimulants in this task are scarce. Objectives. We manipulated the standard 5-CSRTT to determine under which conditions a replicable vigilance decrement could be observed, and sought to determine whether this pattern of changes was sensitive to psychostimulant administration. Methods. One and two-year-old rats performed in five-choice sessions extended to 250 trials. Task difficulty was manipulated by either increasing or decreasing the duration of stimulus presentation, and pre-feeding studies were performed to control for effects of the additional food earned. In the two-year-old group dose-responses were then derived for nicotine (0.1–0.4 mg/kg), amphetamine (0.05–0.4 mg/kg) and caffeine (3–10 mg/kg). Results. Extending five-choice sessions revealed a decline in the performance of two-year-old rats as a function of trial number. Increasing task difficulty induced a response-decrement in one-year old rats; whilst reducing it enhanced the performance of two-year-old rats to that observed in younger subjects. Pre-feeding did not alter the response patterns observed in either group. Nicotine, amphetamine, and caffeine all reversed the performance decrement observed. Conclusions. These results demonstrate that similar performance characteristics can be observed in both human and rat, serving to validate further the 5-CSRTT as a measure of sustained attention. Electronic Publication
Keywords:Amphetamine Nicotine Caffeine Sustained attention Vigilance Five-choice serial reaction time task
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