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Experimental Brain Research

, Volume 133, Issue 1, pp 130–138 | Cite as

Chemical neuromodulation of frontal-executive functions in humans and other animals

  • T.W. Robbins
Review

Abstract.

Neuromodulation of frontal-executive function is reviewed in the context of experiments on rats, monkeys and human subjects. The different functions of the chemically identified systems of the reticular core are analysed from the perspective of their possible different interactions with the prefrontal cortex. The role of dopamine in spatial working memory is reviewed, taking account of its deleterious as well as facilitatory effects. Baseline-dependent effects of dopaminergic manipulation are described in rats on an attentional task, including evidence of enhanced function following infusions of D1 receptor agonists into the prefrontal cortex. The precise nature of the cognitive task under study is shown to be a powerful determinant of the effects of mesofrontal dopamine depletion in monkeys. Parallels are identified in human subjects receiving drugs such as the indirect catecholamine agonists l-dopa, methylphenidate and the dopamine D2 receptor blocker sulpiride. The effects of these drugs on different types of cognitive function sensitive to frontal lobe dysfunction are contrasted with those of a manipulation of 5-HT function, dietary tryptophan depletion. Hypotheses are advanced that accord the ascending systems a greater deal of specificity in modulating prefrontal cortical function than has hitherto been entertained, and clinical and theoretical implications of this hypothesis are discussed.

Prefrontal cortex Orbitofrontal cortex Dorsolateral prefrontal cortex Dopamine Serotonin Noradrenaline Acetylcholine Methylphenidate Executive function Working memory Planning Set shifting 

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Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • T.W. Robbins
    • 1
  1. 1.Department of Experimental Psychology, Downing St., Cambridge CB2 3EB, UKUK

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