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The role of melanin-concentrating hormone in conditioned reward learning

Authors

  • Andrew Sherwood,

    1. Department of Psychological and Brain Sciences, Johns Hopkins University, Ames Hall, 3400 N. Charles Street, Baltimore, MD, USA
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    • A.S., M.W.K. and T.N. contributed equally to this work.

  • Marlena Wosiski-Kuhn,

    1. Department of Psychological and Brain Sciences, Johns Hopkins University, Ames Hall, 3400 N. Charles Street, Baltimore, MD, USA
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    • A.S., M.W.K. and T.N. contributed equally to this work.

  • Truc Nguyen,

    1. Department of Psychological and Brain Sciences, Johns Hopkins University, Ames Hall, 3400 N. Charles Street, Baltimore, MD, USA
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    • A.S., M.W.K. and T.N. contributed equally to this work.

  • Peter C. Holland,

    1. Department of Psychological and Brain Sciences, Johns Hopkins University, Ames Hall, 3400 N. Charles Street, Baltimore, MD, USA
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  • Bernard Lakaye,

    1. Center for Cellular and Molecular Neurobiology, University of Liège, Liège, Belgium
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  • Antoine Adamantidis,

    1. Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, QC, Canada
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  • Alexander W. Johnson

    1. Department of Psychological and Brain Sciences, Johns Hopkins University, Ames Hall, 3400 N. Charles Street, Baltimore, MD, USA
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Dr A. W. Johnson, as above.
E-mail: awj@jhu.edu

Abstract

The orexigenic neuropeptide melanin-concentrating hormone (MCH) is well positioned to play a key role in connecting brain reward and homeostatic systems due to its synthesis in hypothalamic circuitry and receptor expression throughout the cortico-striatal reward circuit. Here we examined whether targeted-deletion of the MCH receptor (MCH-1R) in gene-targeted heterozygote and knockout mice (KO), or systemic treatment with pharmacological agents designed to antagonise MCH-1R in C57BL/6J mice would disrupt two putative consequences of reward learning that rely on different neural circuitries: conditioned reinforcement (CRf) and Pavlovian-instrumental transfer (PIT). Mice were trained to discriminate between presentations of a reward-paired cue (CS+) and an unpaired CS−. Following normal acquisition of the Pavlovian discrimination in all mice, we assessed the capacity for the CS+ to act as a reinforcer for new nose-poke learning (CRf). Pharmacological disruption in control mice and genetic deletion in KO mice impaired CRf test performance, suggesting MCH-1R is necessary for initiating and maintaining behaviors that are under the control of conditioned reinforcers. To examine a dissociable form of reward learning (PIT), a naïve group of mice were trained in separate Pavlovian and instrumental lever training sessions followed by the PIT test. For all mice the CS+ was capable of augmenting ongoing lever responding relative to CS− periods. These results suggest a role for MCH in guiding behavior based on the conditioned reinforcing value of a cue, but not on its incentive motivational value.

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