Stimulation of lateral hypothalamic AMPA receptors may induce feeding in rats

Hettes, Stacey R.; Gonzaga, W. James; Heyming, Theodore; Nguyen, John N.; Perez, Sam D.; Stanley, B. Glenn

doi:10.1016/j.brainres.2010.05.008

Cited by 25 publications

(12 citation statements)

References 35 publications

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“…For example, Leibowitz (1975) used a protocol (Wolf and Yen, 1968) modified from the original method of Klüver and Barrera (1953) to visualize anterior lateral hypothalamic sites where amphetamine suppresses feeding in rats, by labeling cells (using a Nissl stain) and myelin sheaths (using Luxol Fast Blue) in the same tissue (Figure 1H). Finally, extending work done by the Stanley laboratory establishing a role for glutamate and its receptor agonists in feeding control through actions within the lateral hypothalamic area (Stanley et al, 1993a,b,c, 1996; Khan et al, 1999, 2004; Duva et al, 2001, 2002, 2005; Hettes et al, 2003, 2007, 2010; see Stanley et al, 2011), Li et al (2011) have carefully delineated the locations of feeding-sensitive sites for the glutamate receptor agonists NMDA and AMPA by using rigorous methods for situating the locations of their hypothalamic injections that triggered feeding behavior (Figure 1S). …”

Section: The Experimental Control Of Food Intake Using Ici: a Briementioning

confidence: 80%

Controlling feeding behavior by chemical or gene-directed targeting in the brain: what's so spatial about our methods?

Khan

2013

Front. Neurosci.

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Intracranial chemical injection (ICI) methods have been used to identify the locations in the brain where feeding behavior can be controlled acutely. Scientists conducting ICI studies often document their injection site locations, thereby leaving kernels of valuable location data for others to use to further characterize feeding control circuits. Unfortunately, this rich dataset has not yet been formally contextualized with other published neuroanatomical data. In particular, axonal tracing studies have delineated several neural circuits originating in the same areas where ICI injection feeding-control sites have been documented, but it remains unclear whether these circuits participate in feeding control. Comparing injection sites with other types of location data would require careful anatomical registration between the datasets. Here, a conceptual framework is presented for how such anatomical registration efforts can be performed. For example, by using a simple atlas alignment tool, a hypothalamic locus sensitive to the orexigenic effects of neuropeptide Y (NPY) can be aligned accurately with the locations of neurons labeled by anterograde tracers or those known to express NPY receptors or feeding-related peptides. This approach can also be applied to those intracranial “gene-directed” injection (IGI) methods (e.g., site-specific recombinase methods, RNA expression or interference, optogenetics, and pharmacosynthetics) that involve viral injections to targeted neuronal populations. Spatial alignment efforts can be accelerated if location data from ICI/IGI methods are mapped to stereotaxic brain atlases to allow powerful neuroinformatics tools to overlay different types of data in the same reference space. Atlas-based mapping will be critical for community-based sharing of location data for feeding control circuits, and will accelerate our understanding of structure-function relationships in the brain for mammalian models of obesity and metabolic disorders.

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Section: The Experimental Control Of Food Intake Using Ici: a Briementioning

confidence: 80%

Controlling feeding behavior by chemical or gene-directed targeting in the brain: what's so spatial about our methods?

Khan

2013

Front. Neurosci.

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“…The 4 drugs and doses used were as follows: (i) NMDA (5.6 nmol, 2.8 nmol/side); (ii) AMPA (2.1 nmol, 1.1 nmol/side); (iii) NMDA receptor antagonist, D‐AP5 (33.3 nmol, 16.7 nmol/side); and (iv) AMPA receptor antagonist, CNQX disodium salt hydrate (CNQX‐ds; 15.0 nmol, 7.5 nmol/side). While AMPA and CNQX‐ds may act on KA receptors in addition to AMPA receptors (Hettes et al., ), the latter predominate in the LH (Eyigor et al., ; van den Pol et al., ), which leads us to focus on AMPA receptors in the present study. All drugs were purchased from Sigma‐Aldrich Co. (St. Louis, MO) and dissolved in preservative‐free 0.9% NaCl solution (Hospira Inc., Lake Forest, IL) immediately prior to microinjection.…”

Section: Methodsmentioning

confidence: 98%

“…Drugs were delivered through 26‐gauge stainless steel microinjectors with fused silica tubing inside (74 μm ID, 154 μm OD; Polymicro Technologies, Phoenix, AZ) that reached the region of interest (Experiments 1 and 2: V 8.4; Experiment 3: V 8.0). Doses were chosen based on the feeding literature (Hettes et al., ; Stanley et al., , ) and on pilot tests. For Experiment 3, the lower dose of NMDA was used to avoid confounding variables, such as hyperactivity, that may occur in some rats.…”

Section: Methodsmentioning

confidence: 99%

Glutamatergic Input to the Lateral Hypothalamus Stimulates Ethanol Intake: Role of Orexin and Melanin‐Concentrating Hormone

Chen¹,

Barson

Chen

et al. 2012

Alcoholism Clin & Exp Res

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Background Glutamate (GLUT) in the lateral hypothalamus (LH) has been suggested to mediate reward behaviors and may promote the ingestion of drugs of abuse. The current study tested the hypothesis that GLUT in the LH stimulates consumption of ethanol and that this effect occurs, in part, via its interaction with local peptides, hypocretin/orexin (OX) and melanin-concentrating hormone (MCH). Methods In Experiments 1 and 2, male Sprague-Dawley rats, after being trained to drink 9% ethanol, were microinjected in the LH with N-methyl-D-aspartate (NMDA) or its antagonist, D-AP5, or with alpha-amino-5-methyl-3-hydroxy-4-isoxazole propionic acid (AMPA) or its antagonist, CNQX-ds. Consumption of ethanol, chow, and water was then measured. To provide an anatomical control, a separate set of rats was injected 2 mm dorsal to the LH. In Experiment 3, the effect of LH injection of NMDA and AMPA on the expression of OX and MCH was measured using radiolabeled in situ hybridization (ISH) and also digoxigenin-labeled ISH, to distinguish effects on OX and MCH cells in the LH and the nearby perifornical area (PF) and zona incerta (ZI). Results When injected into the LH, NMDA and AMPA both significantly increased ethanol intake while having no effect on chow or water intake. The GLUT receptor antagonists had the opposite effect, significantly reducing ethanol consumption. No effects were observed with injections 2 mm dorsal to the LH. In addition to these behavioral effects, LH injection of NMDA significantly stimulated expression of OX in both the LH and PF while reducing MCH in the ZI, whereas AMPA increased OX only in the LH and had no effect on MCH. Conclusions Glutamatergic inputs to the LH, acting through NMDA and AMPA receptors, appear to have a stimulatory effect on ethanol consumption, mediated in part by increased OX in LH and PF and reduced MCH in ZI.

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“…Activation of the lateral hypothalamus is strongly related to feeding behavior, and this region projects widely throughout the brain. Electrical stimulation of the hypothalamus in sated rats leads to feeding, which terminates once the stimulation is no longer present (Hettes et al, 2010; Stanley et al, 1993; Stanley et al, 1996). In normal, healthy young adults, hypothalamic activation is less following a preload than when fasted (Haase et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Neural correlates of taste and pleasantness evaluation in the metabolic syndrome

et al. 2015

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Metabolic syndrome (MetS) is a constellation of cardiometabolic abnormalities that commonly occur together and increase risk for cardiovascular disease and type II diabetes. Having MetS, especially during middle-age, increases the risk for dementia in later life. Abdominal obesity is a central feature of MetS; therefore, increased efforts to prevent obesity and identify predictors of weight gain are of extreme importance. Altered processing of food reward in the brain of obese individuals has been suggested to be a possible mechanism related to overeating. We scanned fifteen healthy middle-aged controls (aged 44–54) and sixteen middle-aged adults with MetS after a fast (hungry) and after a preload (sated), while they rated the pleasantness of sucrose (sweet) and caffeine (bitter) solutions. Data were analyzed using voxelwise linear mixed-effects modeling, and a region of interest analysis to examine associations between hypothalamic activation to sweet taste and BMI during hunger and satiety. The results indicate that middle-aged individuals with MetS respond with significantly less brain activation than controls without MetS during pleasantness evaluation of sweet and bitter tastes in regions involved in sensory and higher-level taste processing. Participants with higher BMI had greater hypothalamic response during pleasantness evaluation of sucrose in the sated condition. Importantly, this study is the first to document differential brain circuitry in middle-aged adults with MetS, a population at risk for poor physical and cognitive outcomes. Future research aimed at better understanding relationships among MetS, obesity, and brain function is warranted to better conceptualize and develop interventions for overeating in these disorders.

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Stimulation of lateral hypothalamic AMPA receptors may induce feeding in rats

Cited by 25 publications

References 35 publications

Controlling feeding behavior by chemical or gene-directed targeting in the brain: what's so spatial about our methods?

Controlling feeding behavior by chemical or gene-directed targeting in the brain: what's so spatial about our methods?

Glutamatergic Input to the Lateral Hypothalamus Stimulates Ethanol Intake: Role of Orexin and Melanin‐Concentrating Hormone

Neural correlates of taste and pleasantness evaluation in the metabolic syndrome

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