Assessment of sustained attention in ad libitum fed Wistar rats: Effects of MK-801

Abstract

Listen

Translate article

Rationale Rodent models designed to assess cognitive function, such as sustained attention tasks, use food and/or fluid restriction in order to motivate responding. However, evidence indicates that dietary restriction can have profound effects on brain function and on the neurobehavioral effects of drugs. Objective The primary objective of this study was to demonstrate the feasibility of using ad libitum fed rats to assess sustained attention in an operant 2-choice reaction time (2-CRT) task. Because N-methyl- d-aspartate (NMDA) receptor function is critical for sustaining attention in animal models, the effects of the NMDA antagonist MK-801 on 2-CRT performance were also assessed. Methods Male Wistar rats ( n = 20) rats were trained to perform an operant 2-CRT task. A 10% sucrose solution was used as the reinforcer. After performance levels stabilized, the effects of MK-801 (0.01–0.12 mg/kg, IP) were assessed. Results Stable levels of performance on the final version of the 2-CRT task was established after 2–3 months of training. Consistent with prior reports, correct trials varied as a function of stimulus light duration (1000 ms: 67 ± 3%, 500 ms: 59 ± 3%, 100 ms: 51 ± 3%, 50 ms: 43 ± 2%). Administration of 0.06 mg/kg MK-801 significantly increased choice accuracy. Administration of 0.12 mg/kg MK-801 significantly slowed reaction times and resulted in pronounced motor incoordination. Conclusions This study demonstrates that ad libitum fed rats can be trained to perform a 2-CRT task. However, the levels of choice accuracy are lower than typically observed under conditions of dietary restriction. The increase in choice accuracy following MK-801 is consistent with the effects of psychomotor stimulants and may suggest sustained attention was slightly enhanced by MK-801.