title: 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.
authors.affiliation: Merck Sharp and Dohme, The Neuroscience Research Centre, Harlow, Essex, UK.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Waters
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Burnham
authors.forename: Desmond
authors.initials: D
authors.lastname: O'connor
authors.forename: Gerard R
authors.initials: GR
authors.lastname: Dawson
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dias
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D000077408:Modafinil; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010775:Photic Stimulation; D010830:Physostigmine / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology; D012691:Serial Learning / Q000187:drug effects
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D010276:Parasympatholytics; D010277:Parasympathomimetics; D010830:Physostigmine; D012601:Scopolamine; D000077408:Modafinil