The melanin-concentrating hormone (MCH) system in an animal model of depression-like behavior.
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.
Department of Pharmacology, University of California, Irvine, CA, United States. j.garcia@uib.es
M J
MJ
García-Fuster
G S
GS
Parks
S M
SM
Clinton
S J
SJ
Watson
H
H
Akil
O
O
Civelli
D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal; D015415:Biomarkers; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D003863:Depression / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007028:Hypothalamic Hormones / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D008297:Male; D008543:Melanins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D010907:Pituitary Hormones / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction
D015415:Biomarkers; D007028:Hypothalamic Hormones; C491208:MCHR1 protein, rat; D008543:Melanins; D009419:Nerve Tissue Proteins; D010907:Pituitary Hormones; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C019463:melanin-concentrating hormone