Elsevier

Neuroscience

Volume 164, Issue 2, 1 December 2009, Pages 351-359
Neuroscience

Rapid Report
Reduced anticipatory locomotor responses to scheduled meals in ghrelin receptor deficient mice

https://doi.org/10.1016/j.neuroscience.2009.08.009Get rights and content

Abstract

Ghrelin, an orexigenic hormone produced by the stomach, is secreted in anticipation of scheduled meals and in correlation with anticipatory locomotor activity. We hypothesized that ghrelin is directly implicated in stimulating locomotor activity in anticipation of scheduled meals. To test this hypothesis, we observed 24 h patterns of locomotor activity in mice with targeted mutations of the ghrelin receptor gene (GHSR KO) and wild-type littermates, all given access to food for 4 h daily for 14 days. While wild type (WT) and GHSR KO mice produced increases in anticipatory locomotor activity, anticipatory locomotor activity in GHSR KO mice was attenuated (P<0.05). These behavioral measures correlated with attenuated levels of Fos immunoreactivity in a number of hypothalamic nuclei from GHSR KO placed on the same restricted feeding schedule for 7 days and sacrificed at ZT4. Interestingly, seven daily i.p. ghrelin injections mimicked hypothalamic Fos expression patterns to those seen in mice under restricted feeding schedules. These data suggest that ghrelin acts in the hypothalamus to augment locomotor activity in anticipation of scheduled meals.

Section snippets

Animals

Mice with targeted mutations to the ghrelin receptor gene (GHSR KO) and their wild type (WT) littermates were bred at the Carleton University Neuroscience Institute animal facilities. Mice originated from heterozygous breeding pairs obtained from Regeneron Pharmaceuticals in Tarrytown, NY, USA. These mice were generated using a mixed C57bl/J6 and DBA strain as background. Additional mice (C57bl/J6) were obtained from Jackson Laboratories in Bar Harbor, ME, USA. All animals had free access to

Mice show elevated ghrelin concentrations in anticipation of a scheduled meal

As expected, food restricted C57BL/J6 mice adjusted their feeding patterns so as to consume almost all of their normal 24 h food intake during the restricted access period (Interaction effect F(1,14)=4.8, P<0.05; see supplemental Fig. 1, panel A). These animals were capable of doing this within a period of 7 days after the start of the restricted feeding schedule, and consumed more than control animals during the 4 h access period (F(1,14)=198.88, P<0.05; see panel B). Analyses of plasma

Discussion

The coordination of physiological functions and behavioral responses with environmental predictors of food is a critical adaptive feature (Silver and Lesauter, 2008). Environmental cues signaling the proximity of food such as time of day, or a particular place influence a number of peripheral and central mechanisms to generate the behavioral repertoire (i.e. arousal, foraging, risk taking, hoarding, and food consumption) that is necessary to secure the needed nourishment. In this study we

Acknowledgments

This project was funded by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Funds for innovation (CFI) awarded to A.A., and from National Institute of Health (NIH) grant to T.L.H. (DK-060711).

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    These authors contributed equally to this work.

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