Behavioural evidence that modafinil and amphetamine do not produce equivalent qualities of wake promotion in sleep-restricted rats

Abstract

Introduction Performance effects of sleep restriction are generally assessed across three broad domains: cognitive performance, motor performance and mood. Within the domain of cognition, the psychomotor vigilance task (PVT) provides a means to assess vigilant attentional capacity with low cognitive demand, allowing robust deficits following sleep restriction. Using rats, we directly compared equipotent doses of modafinil with amphetamine (in terms of their EEG wake-promoting effects) to access their capacity to reverse attention deficits following 11hrs of sleep restriction. Materials and methods During the PVT task, Reaction Time (RT) latencies are measured to the onset of an imperative light cue that signals food reward, occurring under a variable interval 5s schedule following a houselight preparatory cue. Previous in house studies have demonstrated marked behavioural deficits following 11 h automated biofeedback sleep restriction, where both median RTs slowed and omissions increased. Results Using PVT testing following such a sleep restriction protocol modafinil reversed the effects of sleep restriction with regard to trials completed and omissions. However, there was a pronounced increase in premature responding at the highest dose tested. Administration of amphetamine worsened the behavioural effects of sleep restriction, decreasing trials and increasing response omissions and median response latencies. Both modafinil and amphetamine produced similar wake-promoting effects with regard to EEG measurements. Conclusion In conclusion, these studies demonstrate that simple reaction time measures following sleep restriction can preclinically determine functional differences in wake-promoting compounds that would otherwise remain undetectable using EEG measurements alone. Acknowledgement I’d like to acknowledge Christopher Baxter for his technical involvement in this work.