Ghrelin-deficient mice have fewer orexin cells and reduced cFOS expression in the mesolimbic dopamine pathway under a restricted feeding paradigm

Lamont, Elaine Waddington; Patterson, Zachary R.; Rodrigues, Trevor; Vallejos, O.; Blum, Ian D.; Abizaid, Alfonso

doi:10.1016/j.neuroscience.2012.05.046

Cited by 29 publications

(20 citation statements)

References 43 publications

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“…For example, ghrelin has been implicated in full expression of anticipation of scheduled daily meals and appears to play a role in activating the reward system. Specifically, animals lacking ghrelin have reduced activation of cells (measured by FOS expression) in the ventral tegmental area and nucleus accumbens shell compared to wild-type animals when on feeding schedules (Lamont et al 2012). Areas of the reward system (dorsal striatum and nucleus accumbens) rhythmically express clock genes (Wakamatsu et al 2001), and regularly scheduled daytime meals can shift these rhythms (Angeles-Castellanos et al 2007;Verwey and Amir 2011).…”

Section: Resultsmentioning

confidence: 99%

Circadian Insights into Motivated Behavior

Antle

Silver

2015

Current Topics in Behavioral Neurosciences

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For an organism to be successful in an evolutionary sense, it and its offspring must survive. Such survival depends on satisfying a number of needs that are driven by motivated behaviors, such as eating, sleeping, and mating. An individual can usually only pursue one motivated behavior at a time. The circadian system provides temporal structure to the organism's 24 hour day, partitioning specific behaviors to particular times of the day. The circadian system also allows anticipation of opportunities to engage in motivated behaviors that occur at predictable times of the day. Such anticipation enhances fitness by ensuring that the organism is physiologically ready to make use of a time-limited resource as soon as it becomes available. This could include activation of the sympathetic nervous system to transition from sleep to wake, or to engage in mating, or to activate of the parasympathetic nervous system to facilitate transitions to sleep, or to prepare the body to digest a meal. In addition to enabling temporal partitioning of motivated behaviors, the circadian system may also regulate the amplitude of the drive state motivating the behavior. For example, the circadian clock modulates not only when it is time to eat, but also how hungry we are. In this chapter we explore the physiology of our circadian clock and its involvement in a number of motivated behaviors such as sleeping, eating, exercise, sexual behavior, and maternal behavior. We also examine ways in which dysfunction of circadian timing can contribute to disease states, particularly in psychiatric conditions that include adherent motivational states.

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Section: Resultsmentioning

confidence: 99%

Circadian Insights into Motivated Behavior

Antle

Silver

2015

Current Topics in Behavioral Neurosciences

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“…An earlier study in which the entire NAc was removed did not observe reduced FAA in food restricted rats, indicating that while components of the NAc may participate in expression of FAA, the structure cannot be the source of signals critical for timing FAA [51]. A modulatory role for the NAc is also suggested by the results of recent studies of ghrelin-deficient mice, which expressed less FAA in some studies, and have reduced c-Fos expression in the mesolimbic dopamine pathway under restricted feeding conditions [29]. Our c-Fos data are not consistent with a critical role for the NAc given the extremely low preprandial c-Fos induction in mice on CR.…”

Section: Discussionmentioning

confidence: 98%

“…Measures have included mRNA or protein expression of immediate early genes, such as c-Fos , or clock components like Period 1 or 2 , or metabolic markers such as 2-deoxyglucose uptake in brain sections of rats or mice on daily feeding schedules [25], [26], [27], [28], [29], [30], [31], [32], [33]. These studies have broadly implicated several hypothalamic and a few extrahypothalamic regions as involved in FAA, with some variability in results across studies.…”

Section: Introductionmentioning

confidence: 99%

Behavioral and Neural Correlates of Acute and Scheduled Hunger in C57BL/6 Mice

et al. 2014

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In rodents, daily feeding schedules induce food anticipatory activity (FAA) rhythms with formal properties suggesting mediation by food-entrained circadian oscillators (FEOs). The search for the neuronal substrate of FEOs responsible for FAA is an active area of research, but studies spanning several decades have yet to identify unequivocally a brain region required for FAA. Variability of results across studies leads to questions about underlying biology versus methodology. Here we describe in C57BL/6 male mice the effects of varying the ‘dose’ of caloric restriction (0%, 60%, 80%, 110%) on the expression of FAA as measured by a video-based analysis system, and on the induction of c-Fos in brain regions that have been implicated in FAA. We determined that more severe caloric restriction (60%) leads to a faster onset of FAA with increased magnitude. Using the 60% caloric restriction, we found little evidence for unique signatures of neuronal activation in the brains of mice anticipating a daily mealtime compared to mice that were fasted acutely or fed ad-libitum–even in regions such as the dorsomedial and ventrolateral hypothalamus, nucleus accumbens, and cerebellum that have previously been implicated in FAA. These results underscore the importance of feeding schedule parameters in determining quantitative features of FAA in mice, and demonstrate dissociations between behavioral FAA and neural activity in brain areas thought to harbor FEOs or participate in their entrainment or output.

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“…Furthermore, Blum et al also demonstrated increased activity prior to scheduled mealtime in both wild-type and GHSR knockout mice, although in their study, the response in GHSR knockout mice was attenuated (Blum et al, 2009). Others have also similarly reported that GHSR knockout mice under a restricted feeding paradigm demonstrate attenuated anticipatory locomotor responses and reduced expression of the marker of cellular activation c-fos in the mesolimbic dopamine pathway (Blum et al, 2009; Lamont et al, 2012). Using a different paradigm, Verhagen et al have shown that GHSR knockout mice did not anticipate food when exposed to an activity-based anorexia model, in which mice are given free access to a running wheel and fed once per day for 2 h (Verhagen et al, 2011).…”

Section: Ghrelin and Homeostatic Eatingmentioning

confidence: 94%

Ghrelin and eating behavior: evidence and insights from genetically-modified mouse models

Uchida¹,

Zigman²,

Perelló³

2013

Front. Neurosci.

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Ghrelin is an octanoylated peptide hormone, produced by endocrine cells of the stomach, which acts in the brain to increase food intake and body weight. Our understanding of the mechanisms underlying ghrelin's effects on eating behaviors has been greatly improved by the generation and study of several genetically manipulated mouse models. These models include mice overexpressing ghrelin and also mice with genetic deletion of ghrelin, the ghrelin receptor [the growth hormone secretagogue receptor (GHSR)] or the enzyme that post-translationally modifies ghrelin [ghrelin O-acyltransferase (GOAT)]. In addition, a GHSR-null mouse model in which GHSR transcription is globally blocked but can be cell-specifically reactivated in a Cre recombinase-mediated fashion has been generated. Here, we summarize findings obtained with these genetically manipulated mice, with the aim to highlight the significance of the ghrelin system in the regulation of both homeostatic and hedonic eating, including that occurring in the setting of chronic psychosocial stress.

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Ghrelin-deficient mice have fewer orexin cells and reduced cFOS expression in the mesolimbic dopamine pathway under a restricted feeding paradigm

Cited by 29 publications

References 43 publications

Circadian Insights into Motivated Behavior

Circadian Insights into Motivated Behavior

Behavioral and Neural Correlates of Acute and Scheduled Hunger in C57BL/6 Mice

Ghrelin and eating behavior: evidence and insights from genetically-modified mouse models

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