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An mTph2 SNP gives rise to alterations in extracellular 5-HT levels, but not in performance on a delayed-reinforcement task

Authors

  • Anthony R. Isles,

    1. Laboratory of Cognitive and Behavioural Neuroscience, The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, CB2 4AT, UK
    2. Developmental Psychiatry Section, University of Cambridge, 18a Douglas House, Trumpington Road, Cambridge, UK
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  • Gareth J. Hathway,

    1. Laboratory of Cognitive and Behavioural Neuroscience, The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, CB2 4AT, UK
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    • *

      Present address: Department of Anatomy and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK.

  • Trevor Humby,

    1. Laboratory of Cognitive and Behavioural Neuroscience, The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, CB2 4AT, UK
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  • Carlos De La Riva,

    1. Laboratory of Cognitive and Behavioural Neuroscience, The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, CB2 4AT, UK
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  • Keith M. Kendrick,

    1. Laboratory of Cognitive and Behavioural Neuroscience, The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, CB2 4AT, UK
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  • Lawrence S. Wilkinson

    1. Laboratory of Cognitive and Behavioural Neuroscience, The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, CB2 4AT, UK
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Dr Anthony Isles, 1Laboratory of Cognitive and Behavioural Neuroscience, as above.
E-mail: anthony.isles@bbsrc.ac.uk

Abstract

5-Hydroxytryptamine (5-HT) is an important neurotransmitter mediating many aspects of cognition and behaviour. One psychology in which 5-HT plays an important role is impulsive responding. Recently, we have demonstrated that variation in an aspect of impulsive behaviour, namely delayed gratification, has a clear genetic contribution. Here, we examined the neurobiological relevance of a recently discovered single nucleotide polymorphism (SNP) in the murine gene tryptophan hydroxylase (mTph2) by analysing extracellular levels of 5-HT in medial prefrontal cortex (mPFC) and ventral striatum (VS), key brain regions for impulsive behaviours. The allelic variants were associated with systematic effects on baseline 5-HT efflux in the mPFC and VS. We then went on to examine whether the mTph2 allelic variants gave rise to differences in impulsive behaviour. However, the mTph2 genotype, and therefore presumably baseline brain levels of 5-HT, did not predict impulsive choice, as indexed by sensitivity to delayed reinforcement. Consequently, the data do not support a role for the mTph2 C1473G polymorphism on this aspect of impulsive behaviour. Instead, they indicate that perturbations of the 5-HT system via heritable traits may have differential consequences for qualitatively distinct aspects of impulsive behaviour.

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