Enhanced running wheel activity of both Mch1r- and Pmch-deficient mice

Mchlr-deficient (Mchlrl(-/-)) mice are hyperphagic, hyperactive, lean, and resistant to diet-induced obesity. To examine whether the WHIR is involved in regulating activity-based energy expenditure, we investigated voluntary wheel running (WR) activity of wild-type (WT) and Mchlr(-/-) 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 (Pnich(-/-) mice). Dark cycle WR activity of Mch Ir-/- 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 Mchl(-/-) and WT mice exhibited food anticipatory activity (FAA) before the daily scheduled feeding time, indicating that MCH I R 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 Mchlrl(-)/(-) brain. Importantly, Pinch-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. (C) 2004 Elsevier B.V. All rights reserved.