Melanin-concentrating hormone (MCH) is a bioactive peptide found in 1980 as a modulator of skin coloration in fishes and amphibians. It had not attracted much attention in research until 1995, when it was shown to be induced in genetically obese mice and to be able to increase food intake when injected intracerebroventrically. This made the MCH system a target for anti-obesity drug design, an aim however not feasible for lack of knowledge of the MCH receptor. This changed with our and others discovery of the molecular structure of MCH1 receptor (MCH1R), which propelled the MCH system at the forefront of anti obesity drug research. Our study on the expression profile of the MCH1R however had led to the conclusion that there was much more to the MCH system than only a role in feeding behavior. Of most interest, we had found that the MCH system is predominantly a CNS system and that the highest level of MCH1R expression is in the shell of the nucleus accumbens. We therefore hypothesized that the MCH system may have a role in reward. First, we found that MCH1R KO mice exhibit a reduced cocaine-induced response in the conditioned place preference assay, an indication that the MCH system may regulate motivation for cocaine. This incited us to isolate a MCH1R antagonist to test the acute effects that blockade of the MCH system may have on reward responses. We found that blockade of the MCH system has no effect on food reward but has a profound effect on cocaine reinforcement and reinstatement. These results, although preliminary, point at the MCH system as a novel neuropeptide system involved in modulating drug of abuse related responses. Since reward is known to rely on the dopaminergic system extending from the ventrotegmental area to the nucleus accumbens, we hypothesize that the MCH system evokes its modulatory role by interacting with dopamine receptor positive cells in the shell of the nucleus accumbens and propose to analyze the role of the MCH system in reinforcing behaviors.
If we can demonstrate that the MCH system can regulate the motivational aspect of drugs of abuse, we will have discovered a novel transmitter system involved in addiction. Since we may show that the MCH system may block drug relapse, our data may serve as a basis to use the MCH system as a possible target for helping fight drugs of abuse.
|Wang, Lien; Alachkar, Amal; Sanathara, Nayna et al. (2015) A Methionine-Induced Animal Model of Schizophrenia: Face and Predictive Validity. Int J Neuropsychopharmacol 18:|
|Zhang, Yan; Wang, Chaoran; Wang, Lien et al. (2014) A novel analgesic isolated from a traditional Chinese medicine. Curr Biol 24:117-23|
|Parks, Gregory S; Wang, Lien; Wang, Zhiwei et al. (2014) Identification of neuropeptide receptors expressed by melanin-concentrating hormone neurons. J Comp Neurol 522:3817-33|
|Parks, Gregory S; Olivas, Nicholas D; Ikrar, Taruna et al. (2014) Histamine inhibits the melanin-concentrating hormone system: implications for sleep and arousal. J Physiol 592:2183-96|
|Zhang, Yan; Wang, Chaoran; Guo, Zhimou et al. (2014) Discovery of N-methyltetrahydroprotoberberines with Îº-opioid receptor agonists-opioid receptor agonist activities from corydalis yanhusuo W. T. Wang by using two-dimensional liquid chromatography. J Ethnopharmacol 155:1597-602|
|Long, Zhen; Zhang, Yan; Guo, Zhimou et al. (2014) Amide alkaloids from Scopolia tangutica. Planta Med 80:1124-30|
|Civelli, Olivier; Reinscheid, Rainer K; Zhang, Yan et al. (2013) G protein-coupled receptor deorphanizations. Annu Rev Pharmacol Toxicol 53:127-46|
|Zhang, Li; Parks, Gregory S; Wang, Zhiwei et al. (2013) Anatomical characterization of bombesin receptor subtype-3 mRNA expression in the rodent central nervous system. J Comp Neurol 521:1020-39|
|Garcia-Fuster, M J; Parks, G S; Clinton, S M et al. (2012) The melanin-concentrating hormone (MCH) system in an animal model of depression-like behavior. Eur Neuropsychopharmacol 22:607-13|
|Chung, Shinjae; Liao, Xiao-Hui; Di Cosmo, Caterina et al. (2012) Disruption of the melanin-concentrating hormone receptor 1 (MCH1R) affects thyroid function. Endocrinology 153:6145-54|
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