The role of melanin-concentrating hormone in conditioned reward learning

Andrew Sherwood, Marlena Wosiski-Kuhn, Truc Nguyen, Peter C. Holland, Bernard Lakaye, Antoine Adamantidis, Alexander W. Johnson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3126-3133
Number of pages8
JournalEuropean Journal of Neuroscience
Volume36
Issue number8
DOIs
StatePublished - Oct 2012

Keywords

  • Antagonist
  • Conditioned reinforcement
  • MCH-1R
  • Mice
  • Pavlovian-instrumental transfer

ASJC Scopus subject areas

  • Neuroscience(all)

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