scholarly journals NTS and VTA oxytocin reduces food motivation and food seeking

2020 ◽  
Vol 319 (6) ◽  
pp. R673-R683 ◽  
Author(s):  
Hallie S. Wald ◽  
Ananya Chandra ◽  
Anita Kalluri ◽  
Zhi Yi Ong ◽  
Matthew R. Hayes ◽  
...  
Keyword(s):  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Progressive Ratio ◽  
Food Motivation ◽  
Inhibitory Effects ◽  
Self Administration ◽  
Seeking Behavior ◽  
Operant Reinforcement ◽  
Food Seeking

Oxytocin (OT) is a neuropeptide whose central receptor-mediated actions include reducing food intake. One mechanism of its behavioral action is the amplification of the feeding inhibitory effects of gastrointestinal (GI) satiation signals processed by hindbrain neurons. OT treatment also reduces carbohydrate intake in humans and rodents, and correspondingly, deficits in central OT receptor (OT-R) signaling increase sucrose self-administration. This suggests that additional processes contribute to central OT effects on feeding. This study investigated the hypothesis that central OT reduces food intake by decreasing food seeking and food motivation. As central OT-Rs are expressed widely, a related focus was to assess the role of one or more OT-R-expressing nuclei in food motivation and food-seeking behavior. OT was delivered to the lateral ventricle (LV), nucleus tractus solitarius (NTS), or ventral tegmental area (VTA), and a progressive ratio (PR) schedule of operant reinforcement and an operant reinstatement paradigm were used to measure motivated feeding behavior and food-seeking behavior, respectively. OT delivered to the LV, NTS, or VTA reduced 1) motivation to work for food and 2) reinstatement of food-seeking behavior. Results provide a novel and additional interpretation for central OT-driven food intake inhibition to include the reduction of food motivation and food seeking.

scholarly journals Hindbrain nucleus tractus solitarius glucagon-like peptide-1 receptor signaling reduces appetitive and motivational aspects of feeding

2014 ◽  
Vol 307 (4) ◽  
pp. R465-R470 ◽  
Author(s):  
Amber L. Alhadeff ◽  
Harvey J. Grill
Keyword(s):  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Progressive Ratio ◽  
Ratio Schedule ◽  
Inhibitory Effects ◽  
Medial Nucleus ◽  
Neural Processes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

Central glucagon-like peptide-1 receptor (GLP-1R) signaling reduces food intake by affecting a variety of neural processes, including those mediating satiation, motivation, and reward. While the literature suggests that separable neurons and circuits control these processes, this notion has not been adequately investigated. The intake inhibitory effects of GLP-1R signaling in the hindbrain medial nucleus tractus solitarius (mNTS) have been attributed to interactions with vagally transmitted gastrointestinal satiation signals that are also processed by these neurons. Here, behavioral and pharmacological techniques are used to test the novel hypothesis that the reduction of food intake following mNTS GLP-1R stimulation also results from effects on food-motivated appetitive behaviors. Results show that mNTS GLP-1R activation by microinjection of exendin-4, a long-acting GLP-1R agonist, reduced 1) intake of a palatable high-fat diet, 2) operant responding for sucrose under a progressive ratio schedule of reinforcement and 3) the expression of a conditioned place preference for a palatable food. Together, these data demonstrate that the intake inhibitory effects of mNTS GLP-1R signaling extend beyond satiation and include effects on food reward and motivation that are typically ascribed to midbrain and forebrain neurons.

scholarly journals Medial nucleus tractus solitarius oxytocin receptor signaling and food intake control: the role of gastrointestinal satiation signal processing

2015 ◽  
Vol 308 (9) ◽  
pp. R800-R806 ◽  
Author(s):  
Zhi Yi Ong ◽  
Amber L. Alhadeff ◽  
Harvey J. Grill
Keyword(s):  
Signal Processing ◽  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Oxytocin Receptor ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Medial Nucleus ◽  
A Site ◽  
Intake Control

Central oxytocin (OT) administration reduces food intake and its effects are mediated, in part, by hindbrain oxytocin receptor (OT-R) signaling. The neural substrate and mechanisms mediating the intake inhibitory effects of hindbrain OT-R signaling are undefined. We examined the hypothesis that hindbrain OT-R-mediated feeding inhibition results from an interaction between medial nucleus tractus solitarius (mNTS) OT-R signaling and the processing of gastrointestinal (GI) satiation signals by neurons of the mNTS. Here, we demonstrated that mNTS or fourth ventricle (4V) microinjections of OT in rats reduced chow intake in a dose-dependent manner. To examine whether the intake suppressive effects of mNTS OT-R signaling is mediated by GI signal processing, rats were injected with OT to the 4V (1 μg) or mNTS (0.3 μg), followed by self-ingestion of a nutrient preload, where either treatment was designed to be without effect on chow intake. Results showed that the combination of mNTS OT-R signaling and GI signaling processing by preload ingestion reduced chow intake significantly and to a greater extent than either stimulus alone. Using enzyme immunoassay, endogenous OT content in mNTS-enriched dorsal vagal complex (DVC) in response to ingestion of nutrient preload was measured. Results revealed that preload ingestion significantly elevated endogenous DVC OT content. Taken together, these findings provide evidence that mNTS neurons are a site of action for hindbrain OT-R signaling in food intake control and that the intake inhibitory effects of hindbrain mNTS OT-R signaling are mediated by interactions with GI satiation signal processing by mNTS neurons.

scholarly journals Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

2020 ◽  
Vol 21 (7) ◽  
pp. 2568
Author(s):  
Ujendra Kumar ◽  
Sneha Singh
Keyword(s):  
Food Intake ◽  
Hormonal Regulation ◽  
Critical Role ◽  
Eating Behaviour ◽  
Peripheral Tissues ◽  
Complex Process ◽  
The Many ◽  
The One ◽  
Food Seeking

Obesity is one of the major social and health problems globally and often associated with various other pathological conditions. In addition to unregulated eating behaviour, circulating peptide-mediated hormonal secretion and signaling pathways play a critical role in food intake induced obesity. Amongst the many peptides involved in the regulation of food-seeking behaviour, somatostatin (SST) is the one which plays a determinant role in the complex process of appetite. SST is involved in the regulation of release and secretion of other peptides, neuronal integrity, and hormonal regulation. Based on past and recent studies, SST might serve as a bridge between central and peripheral tissues with a significant impact on obesity-associated with food intake behaviour and energy expenditure. Here, we present a comprehensive review describing the role of SST in the modulation of multiple central and peripheral signaling molecules. In addition, we highlight recent progress and contribution of SST and its receptors in food-seeking behaviour, obesity (orexigenic), and satiety (anorexigenic) associated pathways and mechanism.

The dopamine β-hydroxylase inhibitor, nepicastat, suppresses chocolate self-administration and reinstatement of chocolate seeking in rats

2013 ◽  
Vol 110 (8) ◽  
pp. 1524-1533 ◽  
Author(s):  
Alessandro Zaru ◽  
Paola Maccioni ◽  
Giancarlo Colombo ◽  
Gian Luigi Gessa
Keyword(s):  
Fixed Ratio ◽  
Progressive Ratio ◽  
Schedules Of Reinforcement ◽  
Self Administration ◽  
Pharmacological Agents ◽  
New Class ◽  
Cocaine Seeking ◽  
Reinforcement Measures ◽  
Food Seeking ◽  
Prevention Of Relapse

Craving for chocolate is a common phenomenon, which may evolve to an addictive-like behaviour and contribute to obesity. Nepicastat is a selective dopamine β-hydroxylase (DBH) inhibitor that suppresses cocaine-primed reinstatement of cocaine seeking in rats. We verified whether nepicastat was able to modify the reinforcing and motivational properties of a chocolate solution and to prevent the reinstatement of chocolate seeking in rats. Nepicastat (25, 50 and 100 mg/kg, intraperitoneal) produced a dose-related inhibition of operant self-administration of the chocolate solution in rats under fixed-ratio 10 (FR10) and progressive-ratio schedules of reinforcement, measures of the reinforcing and motivational properties of the chocolate solution, respectively. The effect of nepicastat on the reinstatement of chocolate seeking was studied in rats in which lever-responding had been extinguished by removing the chocolate solution for approximately 8 d. Nepicastat dose-dependently suppressed the reinstatement of lever-responding triggered by a ‘priming’ of the chocolate solution together with cues previously associated with the availability of the reward. In a separate group of food-restricted rats trained to lever-respond for regular food pellets, nepicastat reduced FR10 lever-responding with the same potency as for the chocolate solution. Spontaneous locomotor activity was not modified by nepicastat doses that reduced self-administration of the chocolate solution and regular food pellets and suppressed the reinstatement of chocolate seeking. The results indicate that nepicastat reduces motivation to food consumption sustained by appetite or palatability. Moreover, the results suggest that DBH inhibitors may be a new class of pharmacological agents potentially useful in the prevention of relapse to food seeking in human dieters.

Evidence for the role of dopamine D3receptors in oral operant alcohol self-administration and reinstatement of alcohol-seeking behavior in mice

2007 ◽  
Vol 12 (1) ◽  
pp. 35-50 ◽  
Author(s):  
Christian A. Heidbreder ◽  
Michela Andreoli ◽  
Cristina Marcon ◽  
Daniel M. Hutcheson ◽  
Eliot L. Gardner ◽  
...  
Keyword(s):  
Self Administration ◽  
Seeking Behavior ◽  
Alcohol Seeking

scholarly journals A ventrolateral medulla-midline thalamic circuit for hypoglycemic feeding

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
B. Sofia Beas ◽  
Xinglong Gu ◽  
Yan Leng ◽  
Omar Koita ◽  
Shakira Rodriguez-Gonzalez ◽  
...  
Keyword(s):  
Ventrolateral Medulla ◽  
Cellular Mechanisms ◽  
Posterior Portion ◽  
Functional Connections ◽  
Midline Thalamus ◽  
Anatomical Imaging ◽  
Seeking Behavior ◽  
Catecholamine Neurons ◽  
Food Seeking

AbstractMarked deficits in glucose availability, or glucoprivation, elicit organism-wide counter-regulatory responses whose purpose is to restore glucose homeostasis. However, while catecholamine neurons of the ventrolateral medulla (VLMCA) are thought to orchestrate these responses, the circuit and cellular mechanisms underlying specific counter-regulatory responses are largely unknown. Here, we combined anatomical, imaging, optogenetic and behavioral approaches to interrogate the circuit mechanisms by which VLMCA neurons orchestrate glucoprivation-induced food seeking behavior. Using these approaches, we found that VLMCA neurons form functional connections with nucleus accumbens (NAc)-projecting neurons of the posterior portion of the paraventricular nucleus of the thalamus (pPVT). Importantly, optogenetic manipulations revealed that while activation of VLMCA projections to the pPVT was sufficient to elicit robust feeding behavior in well fed mice, inhibition of VLMCA–pPVT communication significantly impaired glucoprivation-induced feeding while leaving other major counterregulatory responses intact. Collectively our findings identify the VLMCA–pPVT–NAc pathway as a previously-neglected node selectively controlling glucoprivation-induced food seeking. Moreover, by identifying the ventrolateral medulla as a direct source of metabolic information to the midline thalamus, our results support a growing body of literature on the role of the PVT in homeostatic regulation.

scholarly journals Central Nesfatin-1 Reduces Dark-Phase Food Intake and Gastric Emptying in Rats: Differential Role of Corticotropin-Releasing Factor2 Receptor

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 4911-4919 ◽  
Author(s):  
Andreas Stengel ◽  
Miriam Goebel ◽  
Lixin Wang ◽  
Jean Rivier ◽  
Peter Kobelt ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Hypothalamic Nucleus ◽  
Reduce Food Intake ◽  
Dark Phase ◽  
Crf2 Receptor ◽  
Brain Ventricle ◽  
Dose Dependent

Nesfatin-1, derived from nucleobindin2, is expressed in the hypothalamus and reported in one study to reduce food intake (FI) in rats. To characterize the central anorexigenic action of nesfatin-1 and whether gastric emptying (GE) is altered, we injected nesfatin-1 into the lateral brain ventricle (intracerebroventricular, icv) or fourth ventricle (4v) in chronically cannulated rats or into the cisterna magna (intracisternal, ic) under short anesthesia and compared with ip injection. Nesfatin-1 (0.05 μg/rat, icv) decreased 2–3 h and 3–6 h dark-phase FI by 87 and 45%, respectively, whereas ip administration (2 μg/rat) had no effect. The corticotropin-releasing factor (CRF)1/CRF2 antagonist astressin-B or the CRF2 antagonist astressin2-B abolished icv nesfatin-1’s anorexigenic action, whereas an astressin2-B analog, devoid of CRF-receptor binding affinity, did not. Nesfatin-1 icv induced a dose-dependent reduction of GE by 26 and 43% that was not modified by icv astressin2-B. Nesfatin-1 into the 4v (0.05 μg/rat) or ic (0.5 μg/rat) decreased cumulative dark-phase FI by 29 and 60% at 1 h and by 41 and 37% between 3 and 5 h, respectively. This effect was neither altered by ic astressin2-B nor associated with changes in GE. Cholecystokinin (ip) induced Fos expression in 43% of nesfatin-1 neurons in the paraventricular hypothalamic nucleus and 24% of those in the nucleus tractus solitarius. These data indicate that nesfatin-1 acts centrally to reduce dark phase FI through CRF2-receptor-dependent pathways after forebrain injection and CRF2-receptor-independent pathways after hindbrain injection. Activation of nesfatin-1 neurons by cholecystokinin at sites regulating food intake may suggest a role in gut peptide satiation effect.

scholarly journals Ventral tegmental area orexin 1 receptors promote palatable food intake and oppose postingestive negative feedback

2016 ◽  
Vol 311 (3) ◽  
pp. R592-R599 ◽  
Author(s):  
Sarah J. Terrill ◽  
Kellie M. Hyde ◽  
Kristen E. Kay ◽  
Hayden E. Greene ◽  
Calyn B. Maske ◽  
...  
Keyword(s):  
Food Intake ◽  
Ventral Tegmental Area ◽  
Negative Feedback ◽  
Burst Size ◽  
Progressive Ratio ◽  
Ratio Schedule ◽  
Orexin A ◽  
Multiple Test ◽  
Seeking Behavior ◽  
Ventral Tegmental

Hypothalamic orexin neurons project to numerous brain areas, including the ventral tegmental area (VTA), which is involved in motivation and food-seeking behavior. Here we address how exogenously administered orexin-A and endogenous orexin 1 receptor (OX1R) activation in the VTA affects feeding behavior. We hypothesized that orexin-A and OX1R antagonist SB334867 delivered to the VTA, at doses that were subthreshold for effect when injected into the ventricle, would affect intake of palatable foods in multiple test situations. We first used a hedonic feeding model in which satiated rats selectively consume a high-fat diet (HFD). Intra-VTA orexin-A stimulated additional consumption of chow and increased HFD intake in this model. In ad libitum-fed rats given daily 30-min test sessions, intra-VTA orexin-A also increased intake of HFD and 0.1 M sucrose. Further analysis of licking patterns revealed that that VTA orexin-A increased meal size and licking burst size only toward the end of the meal. Consistent with this finding, a subthreshold dose of VTA orexin-A prevented intake suppression induced by gastrointestinal nutrient infusion. Surprisingly, intra-VTA orexin-A had no effect on operant responding for sucrose pellets on a progressive ratio schedule of reinforcement. A role for endogenous VTA OX1R stimulation is supported by our finding that bilateral VTA injection of the selective OX1R antagonist SB334867 suppressed 0.1 M sucrose intake. Together, our data suggest that OX1R activity in the VTA facilitates food intake, potentially by counteracting postingestive negative feedback that would normally suppress feeding later in a meal.

scholarly journals Knockdown of Hypocretin/Orexin Attenuates Extended-Access Cocaine Self-Administration in Rats

2017 ◽  
Author(s):  
Brooke E. Schmeichel ◽  
Alessandra Matzeu ◽  
Pascale Koebel ◽  
Leandro F. Vendruscolo ◽  
Brigitte L. Kieffer ◽  
...  
Keyword(s):  
Stress Responses ◽  
Viral Vector ◽  
Fixed Ratio ◽  
Progressive Ratio ◽  
Ratio Schedule ◽  
Self Administration ◽  
Adult Rats ◽  
Extended Access ◽  
Seeking Behavior ◽  
Melanin Concentrating Hormone

AbstractThe hypocretin/orexin (HCRT) neuropeptide system regulates feeding, arousal state, stress responses, and reward, especially under conditions of enhanced motivational relevance. In particular, HCRT neurotransmission facilitates drug-seeking behavior in circumstances that demand increased effort and/or motivation to take the drug. The present study used a shRNA-encoding adeno-associated viral vector to knockdown Hcrt expression throughout the dorsal hypothalamus in adult rats and determine the role of HCRT in cocaine self-administration. Longterm Hcrt silencing did not impact cocaine self-administration under short-access conditions, but robustly attenuated cocaine intake during extended self-administration access, a model that mimics key features of compulsive cocaine-taking. In addition, Hcrt silencing decreased motivation for both cocaine and palatable food (i.e., sweetened condensed milk; SCM) under a progressive ratio schedule of reinforcement, but did not alter responding for SCM under a fixed ratio schedule. Importantly, Hcrt silencing did not affect food or water consumption, and had no consequence to general measures of arousal-dependent behaviors. At the molecular level, longterm Hcrt knockdown moderately reduced the downstream expression of dynorphin (DYN) and melanin-concentrating hormone (MCH) in the dorsal hypothalamus. These original findings support the hypothesis that HCRT neurotransmission promotes operant responding for both drug and non-drug rewards, preferentially under conditions requiring a high degree of motivation. Furthermore, the current study provides compelling evidence for the involvement of the HCRT system in cocaine self-administration also under low-effort conditions in rats allowed extended access, possibly via functional interactions with DYN and MCH signaling.

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