The role of melanin‐concentrating hormone in conditioned reward learning

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.