Endogenous GLP-1 in lateral septum contributes to stress-induced hypophagia

Terrill, Sarah J.; Maske, Calyn B.; Williams, D.B.

doi:10.1016/j.physbeh.2018.03.001

Cited by 35 publications

(30 citation statements)

References 35 publications

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“…In the rat, we have previously reported that GLP-1R blockade in the dorsal subregion of the LS (dLS) significantly attenuates stress-induced hypophagia [27]. Here, we utilized a mixedmodel design to assess the feeding response to stress in intra-dLS saline and Ex9-treated mice.…”

Section: Study 4: Effects Of Dls Glp-1r Blockade On Stress-induced Hymentioning

confidence: 99%

“…Because the LS has a known role in stress responses [25,26], we investigated the contribution of LS GLP-1R. We reported that in rats, intra-dLS pretreatment with low-dose GLP-1R antagonist attenuated restraint stress-induced hypophagia [27]. Much of the research described above was conducted in rats, and the work that has been done in mice reveals some similarities and several notable species differences.…”

Section: Introductionmentioning

confidence: 99%

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Endogenous GLP-1 in lateral septum promotes satiety and suppresses motivation for food in mice

Terrill

Holt

Maske

et al. 2019

Physiology & Behavior

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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 stressinduced 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.

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Section: Study 4: Effects Of Dls Glp-1r Blockade On Stress-induced Hymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endogenous GLP-1 in lateral septum promotes satiety and suppresses motivation for food in mice

Terrill

Holt

Maske

et al. 2019

Physiology & Behavior

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“…). Finally, blocking GLP‐1R signaling in LS attenuates stress‐induced suppression of feeding (Terrill, Maske, & Williams ). Therefore, it is unclear if changes in drug seeking following LS manipulations are due to alterations in reward or anxiety.…”

Section: Introductionmentioning

confidence: 99%

Lateral septum inhibition reduces motivation for cocaine: Reversal by diazepam

Pantazis

Aston‐Jones

2019

Addiction Biology

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The lateral septum (LS) is a brain region implicated in motivation, addiction, anxiety, and affect. We recently found that LS is necessary for cocaine-seeking behaviors including conditioned place preference and reinstatement of extinguished drug seeking, which involve LS input to limbic regions including ventral tegmental area (VTA) and orexin neurons in hypothalamus. Here, we microinjected baclofen-muscimol (B-M) in LS prior to testing in a behavioral economics (BE) paradigm. We found that intra-LS B-M decreased motivation (increased demand elasticity; α) for cocaine, but did not change consumption at low effort (Q 0 ). We also compared the effects of LS inhibition with the effects of treatment with the benzodiazepine diazepam, which has been shown to facilitate reward pathways and disinhibit VTA dopamine neurons.Pretreatment with diazepam blocked the effects of LS inhibition and restored cocaine demand to that following vehicle treatment. These changes in cocaine demand after LS inhibition or diazepam were not due to effects on anxiety, as both manipulations produced similar effects on anxiety measures but opposing effects on drug taking.Collectively, these studies point to LS as a critical region driving motivation for cocaine, likely through its interactions with the mesolimbic dopamine system.

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“…7 C, D; p=0.0013 and p=0.0004, respectively). Because GLP-1 is involved in the regulation of stress and anxiety (Tauchi et al, 2007;Terrill et al, 2018), we also tested whether re-expression of LepRb on PPG neurons regulates anxiety-like behavior by performance on the elevated zero maze. As expected, LepRb TB/TB mice displayed increased anxiety-like behaviors by increased percent of time spent in the closed arm (Fig.…”

Section: Targeted Expression Of Leprb On Ppg Neurons Does Not Normalimentioning

confidence: 99%

Leptin suppresses development of GLP-1 Inputs to the Paraventricular Nucleus of the Hypothalamus

Biddinger

Lazarenko

Scott

et al. 2020

Preprint

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AbstractThe nucleus of the solitary tract is critical for the central integration of signals from visceral organs and contains preproglucagon (PPG) neurons, which express leptin receptors and send direct projections to the paraventricular nucleus of the hypothalamus (PVH). Here, we visualized neuronal projections of PPG neurons in leptin-deficient Lepob/ob mice and found that projections from PPG neurons are elevated compared with controls, and PPG projections were normalized by targeted rescue of leptin receptors in LepRbTB/TB mice, which lack functional neuronal leptin receptors. Moreover, Lepob/ob and LepRbTB/TB mice displayed increased levels of neuronal activation in the PVH following vagal stimulation, and whole-cell patch recordings of GLP-1 receptor-expressing PVH neurons revealed enhanced excitatory neurotransmission, suggesting that leptin acts cell autonomously to suppress representation of excitatory afferents from PPG neurons, thereby diminishing the impact of visceral sensory information on GLP-1 receptor neurons in the PVH.

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Endogenous GLP-1 in lateral septum contributes to stress-induced hypophagia

Cited by 35 publications

References 35 publications

Endogenous GLP-1 in lateral septum promotes satiety and suppresses motivation for food in mice

Endogenous GLP-1 in lateral septum promotes satiety and suppresses motivation for food in mice

Lateral septum inhibition reduces motivation for cocaine: Reversal by diazepam

Leptin suppresses development of GLP-1 Inputs to the Paraventricular Nucleus of the Hypothalamus

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