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Endogenous GLP-1 in lateral septum promotes satiety and suppresses motivation for food in mice
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Terrill, Sarah J., Holt, Marie K., Maske, Calyn B., Abrams, Nataly, Reimann, Frank, Trapp, Stefan and Williams, Diana L. (2019) Endogenous GLP-1 in lateral septum promotes satiety and suppresses motivation for food in mice. Physiology & Behavior, 206 . pp. 191-199. doi:10.1016/j.physbeh.2019.04.008 ISSN 1873-507X.
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Official URL: http://doi.org/10.1016/j.physbeh.2019.04.008
Abstract
Glucagon-like peptide 1 receptors (GLP-1R) are expressed in the lateral septum (LS) of rats and mice, and we have published that endogenous LS GLP-1 affects feeding and motivation for food in rats. Here we asked if these effects are also observed in mice. In separate dose-response studies using male C57Bl6J mice, intra-LS GLP-1 or the GLP-1R antagonist Exendin 9 (Ex9) was delivered shortly before dark onset, at doses subthreshold for effect when injected intracerebroventricularly (icv). Intra-LS GLP-1 significantly suppressed chow intake early in the dark phase and tended to reduce overnight intake. However, blockade of LS GLP-1R with Ex9 had no effect on ad libitum dark onset chow intake. We then asked if LS GLP-1R blockade blunts nutrient preload-induced intake suppression. Mice were trained to consume Ensure immediately before dark onset, which suppressed subsequent chow intake, and intra-LS Ex9 attenuated that preload-induced intake suppression. We also found that restraint stress robustly activates hindbrain GLP-1-producing neurons, and that LS GLP-1R blockade attenuates 30-min restraint stress-induced hypophagia in mice. Furthermore, we have reported that in the rat, GLP-1R in the dorsal subregion of the LS (dLS) affect motivation for food. We examined this in food-restricted mice responding for sucrose pellets on a progressive ratio (PR) schedule. Intra-dLS GLP-1R stimulation significantly suppressed, and Ex9 significantly increased, operant responding, and the Ex9 effect remained after mice returned to ad libitum conditions. Similarly, we found that stimulation of dLS GLP-1 suppressed licking for sucrose and conversely, Ex9 increased licking under ad libitum feeding conditions. Together, our data suggest that endogenous activation of LS GLP-1R plays a role in feeding in mice under some but not all conditions, and that these receptors strongly influence motivation for food.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
Journal or Publication Title: | Physiology & Behavior | ||||||
Publisher: | Elsevier Inc. | ||||||
ISSN: | 1873-507X | ||||||
Official Date: | 1 July 2019 | ||||||
Dates: |
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Volume: | 206 | ||||||
Page Range: | pp. 191-199 | ||||||
DOI: | 10.1016/j.physbeh.2019.04.008 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Restricted or Subscription Access |
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