Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults

implications for the monoaminergic basis of impulsive behaviour

R. D. Rogers, A. J. Blackshaw, H. C. Middleton, K. Matthews, K. Hawtin, C. Crowley, A. Hopwood, C. Wallace, J. F. W. Deakin, B. J. Sahakian, T. W. Robbins

    Research output: Contribution to journalArticle

    229 Citations (Scopus)

    Abstract

    Rationale: Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour. Objectives and methods: We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the a/a agonist, clonidine (1.5 µg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus- reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions. Results: Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes. Conclusions: These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.
    Original languageEnglish
    Pages (from-to)482-491
    Number of pages10
    JournalPsychopharmacology
    Volume146
    Issue number4
    DOIs
    Publication statusPublished - Oct 1999

    Fingerprint

    Methylphenidate
    Impulsive Behavior
    Reward
    Tryptophan
    Young Adult
    Aptitude
    Clonidine
    Learning
    Prefrontal Cortex
    Catecholamines
    Discrimination Learning
    Risk-Taking
    Cognition
    Reaction Time
    Neurotransmitter Agents
    Motivation
    Serotonin
    Placebos
    Research

    Keywords

    • Adolescent
    • Adrenergic Agents
    • Adult
    • Attention
    • Clonidine
    • Discrimination Learning
    • Double-Blind Method
    • Female
    • Humans
    • Impulsive Behavior
    • Male
    • Methylphenidate
    • Reward
    • Tryptophan

    Cite this

    Rogers, R. D. ; Blackshaw, A. J. ; Middleton, H. C. ; Matthews, K. ; Hawtin, K. ; Crowley, C. ; Hopwood, A. ; Wallace, C. ; Deakin, J. F. W. ; Sahakian, B. J. ; Robbins, T. W. / Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults : implications for the monoaminergic basis of impulsive behaviour. In: Psychopharmacology. 1999 ; Vol. 146, No. 4. pp. 482-491.
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    title = "Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour",
    abstract = "Rationale: Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour. Objectives and methods: We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the a/a agonist, clonidine (1.5 µg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus- reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions. Results: Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes. Conclusions: These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.",
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    Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults : implications for the monoaminergic basis of impulsive behaviour. / Rogers, R. D.; Blackshaw, A. J.; Middleton, H. C.; Matthews, K.; Hawtin, K.; Crowley, C.; Hopwood, A.; Wallace, C.; Deakin, J. F. W.; Sahakian, B. J.; Robbins, T. W.

    In: Psychopharmacology, Vol. 146, No. 4, 10.1999, p. 482-491.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults

    T2 - implications for the monoaminergic basis of impulsive behaviour

    AU - Rogers, R. D.

    AU - Blackshaw, A. J.

    AU - Middleton, H. C.

    AU - Matthews, K.

    AU - Hawtin, K.

    AU - Crowley, C.

    AU - Hopwood, A.

    AU - Wallace, C.

    AU - Deakin, J. F. W.

    AU - Sahakian, B. J.

    AU - Robbins, T. W.

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    AB - Rationale: Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour. Objectives and methods: We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the a/a agonist, clonidine (1.5 µg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus- reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions. Results: Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes. Conclusions: These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.

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    KW - Attention

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    KW - Double-Blind Method

    KW - Female

    KW - Humans

    KW - Impulsive Behavior

    KW - Male

    KW - Methylphenidate

    KW - Reward

    KW - Tryptophan

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