Effects of Endogenous Oxytocin Receptor Signaling in Nucleus Tractus Solitarius on Satiation-Mediated Feeding and Thermogenic Control in Male Rats

Extracellular single-unit recordings from neurons in the area postrema (AP) and the nucleus tractus solitarius (NTS) in anesthetized male rats demonstrated that most cells in these regions have spontaneous activities of 5 Hz or less. Systemic angiotensin (ANG II) (50-500 ng) enhanced the activity of 55% of AP cells tested (n = 76), whereas 53% of tested NTS neurons (n = 62) were inhibited by ANG II. To determine whether these neurons were influenced specifically by circulating ANG II or by the accompanying increase in mean arterial blood pressure (BP), the effects of adrenergic agonists given intravenously on ANG II influenced neurons were also examined. Subsequently two cell types were characterized: cells responding to iv ANG II but not to the adrenergic agonist ("ANG II sensitive") and cells responding in a similar way to both agents ("BP sensitive"). Most ANG II-responsive neurons in the AP (53.5%) and the NTS (65%) were determined to be BP sensitive. These data demonstrate that ANG II influences the activity of AP neurons. In addition, there exists a second population of AP neurons apparently responsive to perturbations of the cardiovascular system. These studies further emphasize the potential roles of the AP in the regulation of body fluid balance.

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Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00075.2011 ◽

2011 ◽

Vol 301 (1) ◽

pp. H230-H240 ◽

Cited By ~ 33

Author(s):

Domitila A. Huber ◽

Ann M. Schreihofer

Keyword(s):

Sympathetic Nerve Activity ◽

Nucleus Tractus Solitarius ◽

Excitatory Input ◽

Rostral Ventrolateral Medulla ◽

Male Rats ◽

Ventrolateral Medulla ◽

Zucker Rats ◽

Caudal Ventrolateral Medulla ◽

Obese Zucker Rats ◽

Altered Regulation

Obese Zucker rats (OZR) have elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) compared with lean Zucker rats (LZR). We examined whether altered tonic glutamatergic, angiotensinergic, or GABAergic inputs to the rostral ventrolateral medulla (RVLM) contribute to elevated SNA and MAP in OZR. Male rats (14–18 wk) were anesthetized with urethane (1.5 g/kg iv), ventilated, and paralyzed to record splanchnic SNA, heart rate (HR), and MAP. Inhibition of the RVLM by microinjections of muscimol eliminated SNA and evoked greater decreases in MAP in OZR vs. LZR ( P < 0.05). Antagonism of angiotensin AT1 receptors in RVLM with losartan yielded modest decreases in SNA and MAP in OZR but not LZR ( P < 0.05). However, antagonism of ionotropic glutamate receptors in RVLM with kynurenate produced comparable decreases in SNA, HR, and MAP in OZR and LZR. Antagonism of GABAA receptors in RVLM with gabazine evoked smaller rises in SNA, HR, and MAP in OZR vs. LZR ( P < 0.05), whereas responses to microinjections of GABA into RVLM were comparable. Inhibition of the caudal ventrolateral medulla, a major source of GABA to the RVLM, evoked attenuated rises in SNA and HR in OZR ( P <0.05). Likewise, inhibition of nucleus tractus solitarius, the major excitatory input to caudal ventrolateral medulla, produced smaller rises in SNA and HR in OZR. These results suggest the elevated SNA and MAP in OZR is derived from the RVLM and that enhanced angiotensinergic activation and reduced GABAergic inhibition of the RVLM may contribute to the elevated SNA and MAP in the OZR.

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Regulation of Oxytocin Receptors and Oxytocin Receptor Signaling

Seminars in Reproductive Medicine ◽

10.1055/s-2006-956775 ◽

2007 ◽

Vol 25 (1) ◽

pp. 052-059 ◽

Cited By ~ 31

Author(s):

Andrew Blanks ◽

Anatoly Shmygol ◽

Steven Thornton

Keyword(s):

Oxytocin Receptor ◽

Receptor Signaling ◽

Oxytocin Receptors

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Oxytocin Receptor Signaling in Myoepithelial and Cancer Cells

Journal of Mammary Gland Biology and Neoplasia ◽

10.1007/s10911-005-9583-7 ◽

2005 ◽

Vol 10 (3) ◽

pp. 221-229 ◽

Cited By ~ 47

Author(s):

Alessandra Reversi ◽

Paola Cassoni ◽

Bice Chini

Keyword(s):

Cancer Cells ◽

Oxytocin Receptor ◽

Receptor Signaling

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Retinoic Acid Stimulates 17β-Estradiol and Testosterone Synthesis in Rat Hippocampal Slice Cultures

Endocrinology ◽

10.1210/en.2008-1644 ◽

2009 ◽

Vol 150 (9) ◽

pp. 4260-4269 ◽

Cited By ~ 56

Author(s):

Eiji Munetsuna ◽

Yasushi Hojo ◽

Minoru Hattori ◽

Hirotaka Ishii ◽

Suguru Kawato ◽

...

Keyword(s):

Retinoic Acid ◽

De Novo ◽

Fold Increase ◽

Retinoid X Receptor ◽

Rat Hippocampus ◽

Male Rats ◽

Receptor Signaling ◽

Retinoic Acids ◽

17Β Estradiol ◽

Testosterone Synthesis

Abstract The hippocampus is essentially involved in learning and memory processes. Its functions are affected by various neuromodulators, including 17β-estradiol, testosterone, and retinoid. Brain-synthesized steroid hormones act as autocrine and paracrine modulators. The regulatory mechanism underlying brain steroidogenesis has not been fully elucidated. Synthesis of sex steroids in the gonads is stimulated by retinoic acids. Therefore, we examined the effects of retinoic acids on estradiol and testosterone biosynthesis in the rat hippocampus. We used cultured hippocampal slices from 10- to 12-d-old male rats to investigate de novo steroidogenesis. The infant rat hippocampus possesses mRNAs for steroidogenic enzymes and retinoid receptors. Slices were used after 24 h of preculture to obtain maximal steroidogenic activity because steroidogenesis in cultured slices decreases with time. The mRNA levels for P45017α, P450 aromatase and estrogen receptor-β in the slices were increased by treatment with 9-cis-retinoic acid but not by all-trans-isomer. The magnitude of stimulation and the shape of the dose-response curve for the mRNA level for P45017α were similar to those for cellular retinoid binding protein type 2, the transcription of which is activated by retinoid X receptor signaling. 9-cis-Retinoic acid also induced a 1.7-fold increase in the protein content of P45017α and a 2-fold increase in de novo synthesis of 17β-estradiol and testosterone. These steroids may be synthesized from a steroid precursor(s), such as pregnenolone or other steroids, or from cholesterol, as so-called neurosteroids. The stimulation of estradiol and testosterone synthesis by 9-cis-retinoic acid might be caused by activation of P45017α transcription via retinoid X receptor signaling.

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Glucagon‐Like Peptide‐1 Receptor Signaling in the Ventral Tegmental Area Reduces Alcohol Self‐Administration in Male Rats

Alcoholism Clinical and Experimental Research ◽

10.1111/acer.14437 ◽

2020 ◽

Cited By ~ 1

Author(s):

Tiarani N. Dixon ◽

Gavan P. McNally ◽

Zhi Yi Ong

Keyword(s):

Ventral Tegmental Area ◽

Male Rats ◽

Receptor Signaling ◽

Self Administration ◽

Glucagon Like Peptide ◽

Ventral Tegmental ◽

Glucagon Like Peptide 1

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Attenuated Dopamine Receptor Signaling in Nucleus Accumbens Core in a Rat Model of Chemically-Induced Neuropathy

10.1101/722801 ◽

2019 ◽

Author(s):

D.E. Selley ◽

M.F. Lazenka ◽

L.J. Sim-Selley ◽

D. N. Potter ◽

Elena H. Chartoff ◽

...

Keyword(s):

Nucleus Accumbens ◽

Dopamine Receptor ◽

Rat Model ◽

Brain Regions ◽

Male Rats ◽

Formalin Injection ◽

Receptor Signaling ◽

Nucleus Accumbens Core ◽

Protein Activation ◽

Chemically Induced

ABSTRACTNeuropathy is major source of chronic pain that can be caused by mechanically or chemically induced nerve injury. Previous work in a rat model of neuropathic pain demonstrated that bilateral formalin injection into the hind paws produced mechanical hypersensitivity (allodynia) and depressed responding for intracranial self-stimulation (ICSS). To determine whether neuropathy alters dopamine receptor responsiveness in mesolimbic brain regions, we examined dopamine D1-like and D2-like receptor (D1/2R) signaling and expression in male rats 14 days after bilateral intraplantar formalin injections into both rear paws. D2R-mediated G-protein activation and expression of the D2R long, but not short, isoform were reduced in nucleus accumbens (NAc) core, but not in NAc shell, caudate-putamen (CPu) or ventral tegmental area (VTA) of formalin-compared to saline-treated rats. In addition, D1R-stimulated adenylyl cyclase (AC) activity was also reduced in NAc core, but not in NAc shell or prefrontal cortex, of formalin-treated rats, whereas D1R expression was unaffected. Expression of other proteins involved in dopamine neurotransmission, including dopamine uptake transporter (DAT) and tyrosine hydroxylase (TH), were unaffected by formalin treatment. In behavioral tests, the effects of D2R agonists on ICSS were attenuated in formalin-treated rats, whereas the effects of D1R agonists were unchanged. These results indicate that intraplantar formalin as a model of chemically induced neuropathy produces attenuation of highly specific DA receptor signaling processes in NAc core of male rats.

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GABA neurons in the nucleus tractus solitarius express GLP-1 receptors and mediate anorectic effects of liraglutide in rats

Science Translational Medicine ◽

10.1126/scitranslmed.aay8071 ◽

2020 ◽

Vol 12 (533) ◽

pp. eaay8071 ◽

Cited By ~ 9

Author(s):

Samantha M. Fortin ◽

Rachele K. Lipsky ◽

Rinzin Lhamo ◽

Jack Chen ◽

Eun Kim ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Nucleus Tractus Solitarius ◽

Area Postrema ◽

Male Rats ◽

Glucagon Like Peptide 1 ◽

Treatment Of Obesity ◽

Cellular Phenotypes ◽

Sites Of Action

The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is approved for the treatment of obesity; however, there is still much to be learned regarding the neuronal sites of action that underlie its suppressive effects on food intake and body weight. Peripherally administered liraglutide in rats acts in part through central GLP-1Rs in both the hypothalamus and the hindbrain. Here, we extend findings supporting a role for hindbrain GLP-1Rs in mediating the anorectic effects of liraglutide in male rats. To dissociate the contribution of GLP-1Rs in the area postrema (AP) and the nucleus tractus solitarius (NTS), we examined the effects of liraglutide in both NTS AAV-shRNA–driven Glp1r knockdown and AP-lesioned animals. Knockdown of NTS GLP-1Rs, but not surgical lesioning of the AP, attenuated the anorectic and body weight–reducing effects of acutely delivered liraglutide. In addition, NTS c-Fos responses were maintained in AP-lesioned animals. Moreover, NTS Glp1r knockdown was sufficient to attenuate the intake- and body weight–reducing effects of chronic daily administered liraglutide over 3 weeks. Development of improved obesity pharmacotherapies requires an understanding of the cellular phenotypes targeted by GLP-1R agonists. Fluorescence in situ hybridization identified Glp1r transcripts in NTS GABAergic neurons, which when inhibited using chemogenetics, attenuated the food intake– and body weight–reducing effects of liraglutide. This work demonstrates the contribution of NTS GLP-1Rs to the anorectic potential of liraglutide and highlights a phenotypically distinct (GABAergic) population of neurons within the NTS that express the GLP-1R and are involved in the mediation of liraglutide signaling.

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