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

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

Previous research has demonstrated cognitive-enhancing effects of modafinil in humans and generated evidence for its therapeutic potential in psychiatric disorders. The neurochemical basis of these effects remains unresolved although a role for α1-adrenoceptors has been hypothesised. In this within-subject, double-blind, placebo-controlled study, 12 healthy male adults received modafinil (300 mg), the α1-adrenoceptor antagonist prazosin (3 mg), 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 α-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 their neurochemical mechanisms. Our findings support the hypothesised involvement of α1-adrenoceptors in some of the cognitive-enhancing effects of modafinil and warrant further investigation.

attention deficit hyperactivity disorder (ADHD), cognition, executive function, human, modafinil, noradrenaline, physiological effects, prazosin, prefrontal cortex, salivary α-amylase
0269-8811
1649-1657
Winder-Rhodes, S. E.
92e9e46f-04a5-4c2d-a16a-cf9828639fbf
Chamberlain, S. R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Idris, M. I.
92a4d72d-0918-4a5a-b390-bbfeb82a0609
Robbins, T. W.
3c01894c-131f-4539-a731-c33854538c47
Sahakian, B. J.
e689cd5c-b84f-4503-86ca-7526cf340121
Müller, U.
a69f6444-728c-4a2e-a000-c5fdab0ab54b
Winder-Rhodes, S. E.
92e9e46f-04a5-4c2d-a16a-cf9828639fbf
Chamberlain, S. R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Idris, M. I.
92a4d72d-0918-4a5a-b390-bbfeb82a0609
Robbins, T. W.
3c01894c-131f-4539-a731-c33854538c47
Sahakian, B. J.
e689cd5c-b84f-4503-86ca-7526cf340121
Müller, U.
a69f6444-728c-4a2e-a000-c5fdab0ab54b

Winder-Rhodes, S. E., Chamberlain, S. R., Idris, M. I., Robbins, T. W., Sahakian, B. J. and Müller, U. (2010) Effects of modafinil and prazosin on cognitive and physiological functions in healthy volunteers. Journal of Psychopharmacology, 24 (11), 1649-1657. (doi:10.1177/0269881109105899).

Record type: Article

Abstract

Previous research has demonstrated cognitive-enhancing effects of modafinil in humans and generated evidence for its therapeutic potential in psychiatric disorders. The neurochemical basis of these effects remains unresolved although a role for α1-adrenoceptors has been hypothesised. In this within-subject, double-blind, placebo-controlled study, 12 healthy male adults received modafinil (300 mg), the α1-adrenoceptor antagonist prazosin (3 mg), 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 α-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 their neurochemical mechanisms. Our findings support the hypothesised involvement of α1-adrenoceptors in some of the cognitive-enhancing effects of modafinil and warrant further investigation.

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More information

Published date: November 2010
Keywords: attention deficit hyperactivity disorder (ADHD), cognition, executive function, human, modafinil, noradrenaline, physiological effects, prazosin, prefrontal cortex, salivary α-amylase

Identifiers

Local EPrints ID: 493044
URI: http://eprints.soton.ac.uk/id/eprint/493044
ISSN: 0269-8811
PURE UUID: f46e8a56-53d2-4327-808d-61747211878b
ORCID for S. R. Chamberlain: ORCID iD orcid.org/0000-0001-7014-8121

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Date deposited: 22 Aug 2024 16:34
Last modified: 23 Aug 2024 01:59

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Contributors

Author: S. E. Winder-Rhodes
Author: S. R. Chamberlain ORCID iD
Author: M. I. Idris
Author: T. W. Robbins
Author: B. J. Sahakian
Author: U. Müller

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