Psychopharmacology (2002) 164:33–41 DOI 10.1007/s00213-002-1174-3 ORIGINAL INVESTIGATION Andrew J. Grottick · Guy A. Higgins Assessing a vigilance decrement in aged rats: effects of pre-feeding, task manipulation, and psychostimulants Received: 24 October 2001 / Accepted: 19 June 2002 / Published online: 24 July 2002  Springer-Verlag 2002 Abstract Rationale: In studies assessing sustained atten- tion in humans, performance is often characterised by a decline in function over time. This response pattern, termed the vigilance decrement, is sensitive to manipu- lations 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. Conclu- sions: 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. Keywords Amphetamine · Nicotine · Caffeine · Sustained attention · Vigilance · Five-choice serial reaction time task Introduction Vigilance enables the maintenance of goal-directed behaviours over time, and as such is a basic process vital to many aspects of perceptual and cognitive function (Parasuraman 1998). In the laboratory, vigilance is assessed in tasks requiring the maintenance of high levels of attention in order to detect aperiodically occurring, rare, or unusual events (Koelega 1993). Performance in these tasks is notable in two respects. Firstly, performance often declines over time, an effect known as the vigilance decrement. This can be indexed both by a progressive decrease in accuracy or stimulus detection, and a slowing of response speed as time on task increases. Secondly, studies in humans demonstrate that psychostimulants including amphetamine, nicotine, and caffeine improve performance, often by reversing a within-session decline in attention (for review, see Koelega 1993). Attempts have been made also to develop procedures in rodents that model particular aspects of attention. One such test is the five-choice serial reaction time task (5- CSRTT; Carli et al. 1983), in which rats are required to detect and respond to lights presented randomly in one of five locations, thus taxing aspects of both divided and sustained attention. Two notable hurdles in the validation of choice reaction time tasks have been a lack of within- session performance changes (Moore et al. 1992; but see Mirza and Stolerman 1998), and their relative insensitiv- A.J. Grottick ( ) ) · G.A. Higgins PRBN-B, F. Hoffmann-La Roche AG, 4070 Basel, Switzerland e-mail: agrottick@arenapharm.com Tel.: +1-858-453 7200 Fax: +1-858-677 0505 A.J. Grottick Arena Pharmaceuticals Inc., 6166 Nancy Ridge Drive, San Diego, CA 92121, USA G.A. Higgins Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA