Inactivation of the melanin concentrating hormone system impairs maternal behavior.
In order to prepare the mother for the demands of pregnancy and lactation, the maternal brain is subjected to a number of adaptations. Maternal behaviors are regulated by complex neuronal interactions. Here, we show that the melanin concentrating hormone (MCH) system is an important regulator of maternal behaviors. First, we report that melanin concentrating hormone receptor 1 knockout (MCHR1 KO) mice display a disruption of maternal behavior. Early postpartum MCHR1 KO females exhibit poor nesting, deficits in pup retrieval and maternal aggression. In addition, ablation of MCH receptors results in decreased milk production and prolactin mRNA levels. Then we show that these results are in line with those obtained in wild type mice (WT) treated with the specific MCHR1 antagonist GW803430. Furthermore, following pups retrieval, MCHR1 KO mice display a lower level of Fos expression than WT mice in the ventral tegmental area, and nucleus accumbens. With the progression of the lactation period, however, the MCHR1 KO mice improve maternal care towards their pups. This is manifested by an increase in the pups׳ survival rate and the decrease in pups׳ retrieval time beyond the second day after parturition. In conclusion, we show that the MCH system plays a significant role in the initiation of maternal behavior. In this context, MCH may play a role in integrating information from multiple sources, and connecting brain reward, homeostatic and regulatory systems.
Departments of Pharmacology, School of Medicine, University of California, 369 Med Surge II, Irvine, CA 92697-4625, United States. Electronic address: aalachka@uci.edu.
Amal
A
Alachkar
Departments of Pharmacology, School of Medicine, University of California, 369 Med Surge II, Irvine, CA 92697-4625, United States.
Lamees
L
Alhassen
Departments of Pharmacology, School of Medicine, University of California, 369 Med Surge II, Irvine, CA 92697-4625, United States.
Zhiwei
Z
Wang
Departments of Pharmacology, School of Medicine, University of California, 369 Med Surge II, Irvine, CA 92697-4625, United States.
Lien
L
Wang
Departments of Pharmacology, School of Medicine, University of California, 369 Med Surge II, Irvine, CA 92697-4625, United States.
Kara
K
Onouye
Departments of Pharmacology, School of Medicine, University of California, 369 Med Surge II, Irvine, CA 92697-4625, United States.
Nayna
N
Sanathara
Departments of Pharmacology, School of Medicine, University of California, 369 Med Surge II, Irvine, CA 92697-4625, United States; Pharmaceutical Sciences, School of Medicine, University of California, 369 Med Surge II, Irvine, CA 92697-4625, United States; Developmental and Cell Biology, School of Medicine, University of California, 369 Med Surge II, Irvine, CA 92697-4625, United States.
Olivier
O
Civelli
D000374:Aggression; D000818:Animals; D000831:Animals, Newborn; D002190:Cannibalism / Q000523:psychology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D007774:Lactation / Q000235:genetics; D008425:Maternal Behavior / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D009425:Nesting Behavior / Q000187:drug effects; D011388:Prolactin / Q000096:biosynthesis; D011744:Pyrimidinones / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D013876:Thiophenes / Q000494:pharmacology
C540748:6-(4-chlorophenyl)-3-(3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl)-3H-thieno(3,2-d)pyrimidin-4-one; C491209:Mchr1 protein, mouse; D011744:Pyrimidinones; D017481:Receptors, Somatostatin; D013876:Thiophenes; D011388:Prolactin
Antagonist; Knockout; Maternal behavior; Melanin concentrating hormone; Mice