Assessment of modafinil on attentional processes in a five-choice serial reaction time test in the rat

Abstract

It is well known that modafinil is an effective wake-promoting agent, but there is growing evidence to suggest that modafinil may also enhance some aspects of cognition. In man, modafinil has been shown to enhance vigilance in sleep-deprived and/or narcoleptic subjects and also to improve executive-type functioning (predominantly inhibitory response control processes) across a variety of human patient population groups. Preclinically, a delay-dependent improvement has been reported with modafinil in a mouse T-maze test of working memory. To investigate further the role of modafinil as a potential cognition enhancer, the effects of modafinil on attentional processes were assessed in the rat. The aim of the present study was to evaluate the potential of modafinil to enhance five-choice serial reaction time test (5-CSRT) performance. Lister Hooded rats received 32-128 mg/kg modafinil and 5-CSRT performance was assessed under standard and test parametric conditions in which the attentional load was increased, and also under conditions of scopolamine pre-treatment. Modafinil failed to significantly enhance 5-CSRT performance under standard conditions. Similarly, modafinil was unable to reverse the deficits in accuracy and/or increased omission errors induced by either parametric or pharmacological manipulations. Indeed, at higher doses, modafinil caused an increase in premature responding under certain test conditions, suggestive of increased impulsivity. The present findings suggest that, although modafinil may enhance vigilance in sleep-deprived human subjects, attentional processes in normal awake rats remain unaffected. No evidence was found to support a modafinil-induced improvement in response control; rather, under conditions of increased attentional load, modafinil appeared to facilitate impulsive responding. Finally, the failure of modafinil to improve a scopolamine-induced performance deficit suggests that modafinil does not act on the cholinergic system directly.

The psychostimulant modafinil facilitates water maze performance and augments synaptic potentiation in dentate gyrus

“…Preclinical studies have also revealed positive effects on neurocognitive performance. Modafinil treatment in normal mice induced a significant improvement in learning and memory, compared to vehicle-treated controls, using spontaneous alternation and serial spatial discrimination T-maze tasks (Beracochea et al, 2001;Beracochea et al, 2003), although it appears to be without effect on the five-choice serial reaction time in rats (Waters et al, 2005).…”

“…10 approximately 30 minutes before the procedures (Waters et al, 2005). The drug preparations were delivered for a total of 16 consecutive days, commencing 7 days before the first water-maze trial, and continuing until the end of the watermaze protocol.…”

“…In contrast, modafinil did not alter the performance on five-choice serial reaction time in rats (Waters et al, 2005). Our first intention was to test the behavioural effect of modafinil by evaluating the performance of drug-treated rats on a spatial learning task.…”

Psychostimulants and Cognition: A Continuum of Behavioral and Cognitive Activation

“…A number of studies have reported increased cognition and attention in humans (Turner et al, 2003;Muller et al, 2004) and rodents (Beracochea et al, 2001(Beracochea et al, , 2002(Beracochea et al, , 2003Ward et al, 2004;Waters et al, 2005;Morgan et al, 2007;Shuman et al, 2009;).…”

The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks

“…This has yet to be supported by controlled studies in experimental animals; for example, Waters et al (2005) found no improvement in rat performance with modafinil on the five-choice serial reaction time test, a well-documented test of attentional control (Robbins 2002). However, the evidence for a specific SSRT-improving role for modafinil suggests that it may also confer non-attentional benefits because the stopsignal task measures a process with relatively low attentional demands, given the salience of the stop signal.…”