4.5 Article

The melanin-concentrating hormone (MCH) system in an animal model of depression-like behavior

Journal

EUROPEAN NEUROPSYCHOPHARMACOLOGY
Volume 22, Issue 8, Pages 607-613

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.euroneuro.2011.12.001

Keywords

Animal model; Depression; Neuropeptide; MCH

Funding

  1. NIH [DA024746]
  2. National Alliance for Research on Schizophrenia and Depression (NARSAD)
  3. Tourette Syndrome Association
  4. NIDA [5P01DA021633-02]
  5. NIMH Conte Center [L99MH6039]
  6. Office of Naval Research (ONR) [N00014-09-1-0598]
  7. Pritzker Neuropsychiatric Research Foundation

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Selective breeding for divergence in locomotion in a novel environment (bHR, bred High-Responder; bLR, bred Low-Responder) correlates with stress-reactivity, spontaneous anxiety-like behaviors and predicts vulnerability in a rodent model of depression. Identifying genetic factors that may account for such vulnerability are key determinants not only for the illness outcome but also for the development of better-tailored treatment options. Melanin-concentrating hormone (MCH) is a neuropeptide that exhibits some of the hallmarks of a regulator of affective states. The aim of this study was to ascertain the role of the MCH system in depression-like behaviors in bHR vs. bLR rats. bLR rats showed a 44% increase in hypothalamic pMCH mRNA and a 14% decrease in hippocampal CA1 MCH1R mRNA when compared to bHR rats. Interestingly, the amount of time that rats spent immobile in the FST (depressive-like behavior) correlated positively with the amount of hypothalamic pMCH mRNA and negatively with that of hippocampal CA1 MCH1R. The results indicate that the bLR bHR is a useful rat model to investigate individual basal genetic differences that participate in the monitoring of emotional responsiveness (i.e., depression- and anxiety-like behaviors). They also point to the MCH system (i.e., chronically higher pMCH expression and consequently receptor down-regulation) as a candidate biomarker for the severity of depressive-like behavior. The data indicate that MCH1R participates in the modulation of depression-like behavior through a process that involves the CA1 region of the hippocampus, supporting the possible use of MCH1R antagonists in the treatment of depression. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.

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