Craig J Slawecki1, Jennifer Roth. 1. The Scripps Research Institute, Department of Neuropharmacology, CVN-14, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. cslawecki@scripps.edu
Abstract
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.
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.