scholarly journals Orexin-A enhances feeding in male rats by activating hindbrain catecholamine neurons

2015 ◽  
Vol 309 (4) ◽  
pp. R358-R367 ◽  
Author(s):  
Ai-Jun Li ◽  
Qing Wang ◽  
Hana Davis ◽  
Rong Wang ◽  
Sue Ritter
Keyword(s):  
Food Intake ◽  
Male Rats ◽  
Ventrolateral Medulla ◽  
Orexin A ◽  
Catecholaminergic Neurons ◽  
Close Proximity ◽  
Cell Groups ◽  
Increase Food Intake ◽  
Catecholamine Neurons ◽  
Positive Direct

Both lateral hypothalamic orexinergic neurons and hindbrain catecholaminergic neurons contribute to control of feeding behavior. Orexin fibers and terminals are present in close proximity to hindbrain catecholaminergic neurons, and fourth ventricular (4V) orexin injections that increase food intake also increase c-Fos expression in hindbrain catecholamine neurons, suggesting that orexin neurons may stimulate feeding by activating catecholamine neurons. Here we examine that hypothesis in more detail. We found that 4V injection of orexin-A (0.5 nmol/rat) produced widespread activation of c-Fos in hindbrain catecholamine cell groups. In the A1 and C1 cell groups in the ventrolateral medulla, where most c-Fos-positive neurons were also dopamine β hydroxylase (DBH) positive, direct injections of a lower dose (67 pmol/200 nl) of orexin-A also increased food intake in intact rats. Then, with the use of the retrogradely transported immunotoxin, anti-DBH conjugated to saporin (DSAP), which targets and destroys DBH-expressing catecholamine neurons, we examined the hypothesis that catecholamine neurons are required for orexin-induced feeding. Rats given paraventricular hypothalamic injections of DSAP, or unconjugated saporin (SAP) as control, were implanted with 4V or lateral ventricular (LV) cannulas and tested for feeding in response to ventricular injection of orexin-A (0.5 nmol/rat). Both LV and 4V orexin-A stimulated feeding in SAP controls, but DSAP abolished these responses. These results reveal for the first time that catecholamine neurons are required for feeding induced by injection of orexin-A into either LV or 4V.

scholarly journals Activation of catecholamine neurons in the ventral medulla reduces CCK-induced hypophagia and c-Fos activation in dorsal medullary catecholamine neurons

2018 ◽  
Vol 315 (3) ◽  
pp. R442-R452
Author(s):  
Ai-Jun Li ◽  
Qing Wang ◽  
Sue Ritter
Keyword(s):  
Food Intake ◽  
Ventrolateral Medulla ◽  
Designer Drug ◽  
Cell Group ◽  
Cell Groups ◽  
Increase Food Intake ◽  
Threatening Condition ◽  
Metabolic Conditions ◽  
Fos Expression ◽  
Catecholamine Neurons

Catecholamine (CA) neurons within the A1 and C1 cell groups in the ventrolateral medulla (VLM) potently increase food intake when activated by glucose deficit. In contrast, CA neurons in the A2 cell group of the dorsomedial medulla are required for reduction of food intake by cholecystokinin (CCK), a peptide that promotes satiation. Thus dorsal and ventral medullary CA neurons are activated by divergent metabolic conditions and mediate opposing behavioral responses. Acute glucose deficit is a life-threatening condition, and increased feeding is a key response that facilitates survival of this emergency. Thus, during glucose deficit, responses to satiation signals, like CCK, must be suppressed to ensure glucorestoration. Here we test the hypothesis that activation of VLM CA neurons inhibits dorsomedial CA neurons that participate in satiation. We found that glucose deficit produced by the antiglycolytic glucose analog, 2-deoxy-d-glucose, attenuated reduction of food intake by CCK. Moreover, glucose deficit increased c-Fos expression by A1 and C1 neurons while reducing CCK-induced c-Fos expression in A2 neurons. We also selectively activated A1/C1 neurons in TH-Cre+ transgenic rats in which A1/C1 neurons were transfected with a Cre-dependent designer receptor exclusively activated by a designer drug (DREADD). Selective activation of A1/C1 neurons using the DREADD agonist, clozapine- N-oxide, attenuated reduction of food intake by CCK and prevented CCK-induced c-Fos expression in A2 CA neurons, even under normoglycemic conditions. Results support the hypothesis that activation of ventral CA neurons attenuates satiety by inhibiting dorsal medullary A2 CA neurons. This mechanism may ensure that satiation does not terminate feeding before restoration of normoglycemia.

scholarly journals Hindbrain Oxytocin Receptors Contribute to the Effects of Circulating Oxytocin on Food Intake in Male Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2845-2857 ◽  
Author(s):  
Jacqueline M. Ho ◽  
Vishwanath T. Anekonda ◽  
Benjamin W. Thompson ◽  
Mingyan Zhu ◽  
Robert W. Curry ◽  
...  
Keyword(s):  
Food Intake ◽  
Male Rats ◽  
Predominant Role ◽  
Catecholaminergic Neurons ◽  
Downstream Target ◽  
Oxytocin Receptors ◽  
Electrophysiological Studies ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Catecholamine Neurons

Oxytocin (OT)-elicited hypophagia has been linked to neural activity in the nucleus of the solitary tract (NTS). Because plasma OT levels increase after a meal, we hypothesized that circulating OT acts at both peripheral and hindbrain OT receptors (OTRs) to limit food intake. To initially determine whether circulating OT inhibits food intake by acting at hindbrain OTRs, we pretreated rats with an OTR antagonist administered into the fourth ventricle (4V) followed by either central or systemic OT administration. Administration of the OTR antagonist into the 4V blocked anorexia induced by either 4V or ip injection of OT. However, blockade of peripheral OTRs also weakened the anorectic response to ip OT. Our data suggest a predominant role for hindbrain OTRs in the hypophagic response to peripheral OT administration. To elucidate central mechanisms of OT hypophagia, we tested whether OT activates NTS catecholaminergic neurons. OT (ip) increased the number of NTS cells expressing c-Fos, of which 10%–15% were catecholaminergic. Furthermore, electrophysiological studies in mice revealed that OT stimulated 47% (8 of 17) of NTS catecholamine neurons through a presynaptic mechanism. However, OT-elicited hypophagia did not appear to require activation of α1-adrenoceptors, and blockade of glucagon-like peptide-1 receptors similarly did not attenuate anorexia induced by OT. These findings demonstrate that OT elicits satiety through both central and peripheral OTRs and that although catecholamine neurons are a downstream target of OT signaling in the NTS, the hypophagic effect is mediated independently of α1-adrenoceptor signaling.

scholarly journals Acute systemic hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the caudal ventrolateral medulla

2013 ◽  
Vol 305 (10) ◽  
pp. R1112-R1123 ◽  
Author(s):  
T. Luise King ◽  
David D. Kline ◽  
Brian C. Ruyle ◽  
Cheryl M. Heesch ◽  
Eileen M. Hasser
Keyword(s):  
Paraventricular Nucleus ◽  
Acute Hypoxia ◽  
Hypothalamic Paraventricular Nucleus ◽  
Ventrolateral Medulla ◽  
Caudal Ventrolateral Medulla ◽  
Catecholaminergic Neurons ◽  
Systemic Hypoxia ◽  
Neuroendocrine Responses ◽  
Catecholamine Neurons ◽  
Catecholaminergic Cells

Hypoxia activates catecholamine neurons in the caudal ventrolateral medulla (CVLM). The hypothalamic paraventricular nucleus (PVN) modulates arterial chemoreflex responses and receives catecholaminergic projections from the CVLM, but it is not known whether the CVLM-PVN projection is activated by chemoreflex stimulation. We hypothesized that acute hypoxia (AH) activates PVN-projecting catecholaminergic neurons in the CVLM. Fluoro-Gold (2%, 60–90 nl) was microinjected into the PVN of rats to retrogradely label CVLM neurons. After recovery, conscious rats underwent 3 h of normoxia (21% O2, n = 4) or AH (12, 10, or 8% O2; n = 5 each group). We used Fos immunoreactivity as an index of CVLM neuronal activation and tyrosine hydroxylase (TH) immunoreactivity to identify catecholaminergic neurons. Positively labeled neurons were counted in six caudal-rostral sections containing CVLM. Hypoxia progressively increased the number of Fos-immunoreactive CVLM cells (21%, 19 ± 6; 12%, 49 ± 2; 10%, 117 ± 8; 8%, 179 ± 7; P < 0.001). Catecholaminergic cells colabeled with Fos immunoreactivity in the CVLM were observed following 12% O2, and further increases in hypoxia severity caused markedly more activation. PVN-projecting CVLM cells were activated following more severe hypoxia (10% and 8% O2). A large proportion (89 ± 3%) of all activated PVN-projecting CVLM neurons were catecholaminergic, regardless of hypoxia intensity. Data suggest that catecholaminergic, PVN-projecting CVLM neurons are particularly hypoxia-sensitive, and these neurons may be important in the cardiorespiratory and/or neuroendocrine responses elicited by the chemoreflex.

scholarly journals Dorsomedial hypothalamic NPY affects cholecystokinin-induced satiety via modulation of brain stem catecholamine neuronal signaling

2016 ◽  
Vol 311 (5) ◽  
pp. R930-R939 ◽  
Author(s):  
Claire B. de La Serre ◽  
Yonwook J. Kim ◽  
Timothy H. Moran ◽  
Sheng Bi
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Neural Systems ◽  
Adeno Associated Virus ◽  
Dorsomedial Hypothalamus ◽  
Neuronal Signaling ◽  
Catecholaminergic Neurons ◽  
Nucleus Of Solitary Tract ◽  
Close Proximity ◽  
Feeding Effects

Increased neuropeptide Y (NPY) gene expression in the dorsomedial hypothalamus (DMH) has been shown to cause hyperphagia, but the pathway underlying this effect remains less clear. Hypothalamic neural systems play a key role in the control of food intake, in part, by modulating the effects of meal-related signals, such as cholecystokinin (CCK). An increase in DMH NPY gene expression decreases CCK-induced satiety. Since activation of catecholaminergic neurons within the nucleus of solitary tract (NTS) contributes to the feeding effects of CCK, we hypothesized that DMH NPY modulates NTS neural catecholaminergic signaling to affect food intake. We used an adeno-associated virus system to manipulate DMH NPY gene expression in rats to examine this pathway. Viral-mediated hrGFP anterograde tracing revealed that DMH NPY neurons project to the NTS; the projections were in close proximity to catecholaminergic neurons, and some contained NPY. Viral-mediated DMH NPY overexpression resulted in an increase in NPY content in the NTS, a decrease in NTS tyrosine hydroxylase (TH) expression, and reduced exogenous CCK-induced satiety. Knockdown of DMH NPY produced the opposite effects. Direct NPY administration into the fourth ventricle of intact rats limited CCK-induced satiety and overall TH phosphorylation. Taken together, these results demonstrate that DMH NPY descending signals affect CCK-induced satiety, at least in part, via modulation of NTS catecholaminergic neuronal signaling.

Effects of activation and blockade of orexin A receptors in the medial preoptic area on food intake in male rats

2015 ◽  
Vol 604 ◽  
pp. 157-160 ◽  
Author(s):  
Abdolrahman Sarihi ◽  
Amir Hossein Emam ◽  
Mohammad Hosseini Panah ◽  
Alireza Komaki ◽  
Sadegh Seif ◽  
...  
Keyword(s):  
Food Intake ◽  
Preoptic Area ◽  
Medial Preoptic Area ◽  
Male Rats ◽  
Orexin A

scholarly journals Evidence for the role of hindbrain orexin-1 receptors in the control of meal size

2011 ◽  
Vol 301 (6) ◽  
pp. R1692-R1699 ◽  
Author(s):  
Eric M. Parise ◽  
Nicole Lilly ◽  
Kristen Kay ◽  
Amanda M. Dossat ◽  
Rohit Seth ◽  
...  
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Dark Phase ◽  
Dark Cycle ◽  
Orexin A ◽  
Increase Food Intake ◽  
Double Label ◽  
Increased Activity ◽  
4Th Ventricle

Hypothalamic orexin neurons project to the hindbrain, and 4th-ventricle intracerebroventricular (4th-icv) injection of orexin-A treatment increases food intake. We assessed the effects of hindbrain orexin-A and the orexin-1-receptor antagonist SB334867 on meal pattern in rats consuming standard chow. When injected 4th-icv shortly before dark onset, lower doses of orexin-A increased food intake over a 2-h period by increasing the size of the first meal relative to vehicle, whereas the highest dose increased food intake by causing the second meal to be taken sooner. Conversely, hindbrain SB334867 reduced food intake by decreasing the size of the first meal of the dark phase. We also examined the effects of 4th-icv orexin-A and SB334867 on locomotor activity. Only the highest dose of orexin-A increased activity, and SB334867 had no effect. In addition, hindbrain SB334867 induced c-Fos in the nucleus of the solitary tract. These data support the suggestion that endogenous hindbrain orexin-A acts to limit satiation. Both orexin-A and the pancreatic satiation hormone amylin require an intact area postrema to affect food intake, so we asked whether 4th-icv orexin-A impairs the satiating effect of peripheral amylin treatment. Amylin reduced the size of the first meal of the dark cycle when rats were pretreated with 4th-icv saline, yet amylin was ineffective after 4th-icv orexin-A pretreatment. Using double-label immunohistochemistry, we determined that some orexin-A fibers in the area postrema are located in proximity to amylin-responsive neurons. Therefore, hindbrain orexin-A may increase food intake, in part, by reducing the ability of rats to respond to amylin during a meal.

scholarly journals NPY2 receptor activation in the dorsal vagal complex increases food intake and attenuates CCK-induced satiation in male rats

2019 ◽  
Vol 316 (4) ◽  
pp. R406-R416
Author(s):  
Nathaneal J. Huston ◽  
Lynne A. Brenner ◽  
Zachary C. Taylor ◽  
Robert C. Ritter
Keyword(s):  
Food Intake ◽  
Peptide Yy ◽  
Receptor Activation ◽  
Vagal Afferents ◽  
Male Rats ◽  
Dorsal Vagal Complex ◽  
Increase Food Intake ◽  
Control Food ◽  
Intracerebroventricular Injections ◽  
Control Food Intake

Neuropeptide Y (NPY), peptide YY (PYY), and their cognate receptors (YR) are expressed by subpopulations of central and peripheral nervous system neurons. Intracerebroventricular injections of NPY or PYY increase food intake, and intrahypothalamic NPY1 or NPY5 receptor agonist injections also increase food intake. In contrast, injection of PYY in the periphery reduces food intake, apparently by activating peripheral Y2R. The dorsal vagal complex (DVC) of the hindbrain is the site where vagal afferents relay gut satiation signals to the brain. While contributions of the DVC are increasingly investigated, a role for DVC YR in control of food intake has not been examined systematically. We used in situ hybridization to confirm expression of Y1R and Y2R, but not Y5R, in the DVC and vagal afferent neurons. We found that nanoinjections of a Y2R agonist, PYY-(3–36), into the DVC significantly increased food intake over a 4-h period in satiated male rats. PYY-(3–36)-evoked food intake was prevented by injection of a selective Y2R antagonist. Injection of a Y1R/Y5R-preferring agonist into the DVC failed to increase food intake at doses reported to increase food intake following hypothalamic injection. Finally, injection of PYY-(3–36) into the DVC prevented reduction of 30-min food intake following intraperitoneal injection of cholecystokinin (CCK). Our results indicate that activation of DVC Y2R, unlike hypothalamic or peripheral Y2R, increases food intake. Furthermore, in the context of available electrophysiological observations, our results are consistent with the hypothesis that DVC Y2R control food intake by dampening vagally mediated satiation signals in the DVC.

scholarly journals Catecholaminergic neurons projecting to the paraventricular nucleus of the hypothalamus are essential for cardiorespiratory adjustments to hypoxia

2015 ◽  
Vol 309 (7) ◽  
pp. R721-R731 ◽  
Author(s):  
T. Luise King ◽  
Brian C. Ruyle ◽  
David D. Kline ◽  
Cheryl M. Heesch ◽  
Eileen M. Hasser
Keyword(s):  
Paraventricular Nucleus ◽  
Minute Ventilation ◽  
Sensory Information ◽  
Ventrolateral Medulla ◽  
Arterial Oxygen ◽  
Catecholaminergic Neurons ◽  
Ventilatory Responses ◽  
Cardiorespiratory Function ◽  
Neuroendocrine Responses ◽  
Catecholamine Neurons

Brainstem catecholamine neurons modulate sensory information and participate in control of cardiorespiratory function. These neurons have multiple projections, including to the paraventricular nucleus (PVN), which contributes to cardiorespiratory and neuroendocrine responses to hypoxia. We have shown that PVN-projecting catecholaminergic neurons are activated by hypoxia, but the function of these neurons is not known. To test the hypothesis that PVN-projecting catecholamine neurons participate in responses to respiratory challenges, we injected IgG saporin (control; n = 6) or anti-dopamine β-hydroxylase saporin (DSAP; n = 6) into the PVN to retrogradely lesion catecholamine neurons projecting to the PVN. After 2 wk, respiratory measurements (plethysmography) were made in awake rats during normoxia, increasing intensities of hypoxia (12, 10, and 8% O2) and hypercapnia (5% CO2-95% O2). DSAP decreased the number of tyrosine hydroxylase-immunoreactive terminals in PVN and cells counted in ventrolateral medulla (VLM; −37%) and nucleus tractus solitarii (nTS; −36%). DSAP produced a small but significant decrease in respiratory rate at baseline (during normoxia) and at all intensities of hypoxia. Tidal volume and minute ventilation (VE) index also were impaired at higher hypoxic intensities (10-8% O2; e.g., VE at 8% O2: IgG = 181 ± 22, DSAP = 91 ± 4 arbitrary units). Depressed ventilation in DSAP rats was associated with significantly lower arterial O2 saturation at all hypoxic intensities. PVN DSAP also reduced ventilatory responses to 5% CO2 (VE: IgG = 176 ± 21 and DSAP = 84 ± 5 arbitrary units). Data indicate that catecholamine neurons projecting to the PVN are important for peripheral and central chemoreflex respiratory responses and for maintenance of arterial oxygen levels during hypoxic stimuli.

2-arachidonylglycerol interacts with nitric oxide in the dorsomedial hypothalamus to increase food intake and body weight in young male rats

2019 ◽  
Vol 698 ◽  
pp. 27-32 ◽  
Author(s):  
Jacob J. McGavin ◽  
Nicholas L. Cochkanoff ◽  
Emily I. Poole ◽  
Karen M. Crosby
Keyword(s):  
Nitric Oxide ◽  
Body Weight ◽  
Food Intake ◽  
Young Male ◽  
Male Rats ◽  
Dorsomedial Hypothalamus ◽  
Increase Food Intake

scholarly journals Ghrelin Stimulates GH But Not Food Intake in Arcuate Nucleus Ablated Rats

Endocrinology ◽  
2002 ◽  
Vol 143 (9) ◽  
pp. 3268-3275 ◽  
Author(s):  
Hideki Tamura ◽  
Jun Kamegai ◽  
Takako Shimizu ◽  
Shinya Ishii ◽  
Hitoshi Sugihara ◽  
...  
Keyword(s):  
Food Intake ◽  
Normal Control ◽  
Arcuate Nucleus ◽  
Monosodium Glutamate ◽  
Male Rats ◽  
Appetite Control ◽  
Gh Secretion ◽  
Increase Food Intake ◽  
Hypothalamic Arcuate Nucleus ◽  
Plasma Gh

Abstract Ghrelin, an endogenous ligand for the GH secretagogue receptor 1a (GHS-R1a), was originally purified from the rat stomach. Ghrelin mRNA and peptide have also been detected in the hypothalamus and pituitary. Ghrelin is a novel acylated peptide that regulates GH release and energy metabolism. GHS-R1a mRNA is expressed in the pituitary gland as well as in several areas of the brain including the hypothalamus. In this study, we examined whether ghrelin could stimulate GH secretion and feeding in chronic GHRH, neuropeptide Y, and agouti-related protein deficient rats that were neonatally treated with monosodium glutamate (MSG), which destroys the neurons in the hypothalamic arcuate nucleus (ARC). Intravenous (iv) administration of rat ghrelin (10 μg/kg body weight) increased plasma GH levels significantly in the normal adult male rats during a GH trough period of pulsatile GH secretion, while iv injection of ghrelin in MSG-treated rats resulted in a markedly attenuated GH response. When rat ghrelin (10 μg/rat) was administered intracerebroventricular (icv), plasma GH levels were increased comparably in normal control and MSG-treated rats. However, the GH release after icv injection of ghrelin was markedly diminished compared with that after iv administration of a small amount of ghrelin in normal control rats (icv: 10 μg/rat, iv: approximately 4.0 μg/rat), indicating that the GH-releasing activity of exogenous ghrelin is route dependent and at least in part via hypothalamic ARC. The icv administration of 1 μg of ghrelin increased significantly 4-h food intake in normal control, whereas the peptide did not increase food intake in MSG-treated rats, indicating that the feeding response to ghrelin requires intact ARC. Taken together, the primary action of ghrelin on appetite control and GH releasing activity is via the ARC even though it might act on another type of GHS-R besides GHS-R1a.

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