Effects of modafinil and prazosin on cognitive and physiological functions in healthy volunteers

Previous research has demonstrated cognitive-enhancing effects of modafinil in patients with neuropsychiatric disorders and healthy volunteers. The neurochemical basis of these effects remains unresolved although a role for alpha1-adrenoceptors has been hypothesized. In this within-subject, double-blind, placebo-controlled study, twelve healthy male adults received modafinil (300mg), the alpha1-adrenoceptor antagonist prazosin (3mg), both together and placebo on separate occasions at least 5 days apart. Cognitive effects were assessed using a well-validated testing battery focusing on executive and working memory functions. Blood pressure, heart rate and salivary alpha-amylase (sAA) were measured at hourly intervals. Cognitive effects of modafinil and prazosin were identified at the difficult levels of the One-Touch Stockings of Cambridge (OTSOC) planning task. Prazosin antagonized the error-reducing effect of modafinil when the agents were given together. In contrast, the combined agents acted synergistically to increase time taken to complete OTSOC problems compared with placebo. The tachycardic and sAA-elevating effects of prazosin were also potentiated by concurrent modafinil administration. The current data suggest that the cognitive effects of modafinil on performance accuracy and latency are dissociable in terms of its neurochemical mechanisms. Our findings support the hypothesized involvement of alpha1-adrenoceptors in some of the cognitive-enhancing effects of moddafinil.