Enhanced running wheel activity of both Mch1r- and Pmch-deficient mice.
Mch1r-deficient (Mch1r(-/-)) mice are hyperphagic, hyperactive, lean, and resistant to diet-induced obesity. To examine whether the MCH1R is involved in regulating activity-based energy expenditure, we investigated voluntary wheel running (WR) activity of wild-type (WT) and Mch1r(-/-) mice basally, in response to diets with different caloric density and with different feeding schedules. We also evaluated WR activity of mice with ablation of the prepro-MCH gene (Pmch(-/-) mice). Dark cycle WR activity of Mch1r(-/-) mice fed low fat (LF) chow was increased significantly relative to WT mice. Transition to moderate high-fat (MHF) diet was associated with an increase in nocturnal WR activity in both genotypes. Both Mch1r(-/-) and WT mice exhibited food anticipatory activity (FAA) before the daily scheduled feeding time, indicating that MCH1R is not required for FAA. Naloxone (3 mg/kg, i.p.) suppressed WR activity of both genotypes, suggesting opioid regulation of locomotor activity. WR increased nocturnal dynorphin mRNA levels in Mch1r(-/-) brain. Importantly, Pmch-deficient mice had significantly enhanced WR activity relative to WT controls. These results suggest that endogenous MCH plays an inhibitory role in regulating locomotor activity. In summary, we demonstrated enhanced WR activities in mice lacking either MCH or its cognate receptor.
Zhou
Dan
D
Department of Pharmacology, Merck Research Laboratories, RY80Y-150, Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Shen
Zhu
Z
Strack
Alison M
AM
Marsh
Donald J
DJ
Shearman
Lauren P
LP
D000818:Animals; D001921:Brain / Q000378:metabolism; D004704:Endocrinology; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D007028:Hypothalamic Hormones / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D011498:Protein Precursors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
D007028:Hypothalamic Hormones; C491209:Mchr1 protein, mouse; D011498:Protein Precursors; D017481:Receptors, Somatostatin; C059991:melanin-concentrating hormone precursors; D009270:Naloxone