Central oxytocin signaling inhibits food reward-motivated behaviors and VTA dopamine responses to food-predictive cues in male rats

Liu, Clarissa M.; Hsu, Ted M.; Suarez, Andrea N.; Subramanian, Keshav S.; Fatemi, Ryan A.; Cortella, Alyssa M.; Noble, Emily E.; Roitman, Mitchell F.; Kanoski, Scott E.

doi:10.1016/j.yhbeh.2020.104855

Cited by 17 publications

(29 citation statements)

References 86 publications

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“…Indeed, about 10% of OT-R-expressing VTA neurons are dopaminergic and these neurons project to the ACB [ 65 ]. Recent evidence from our group revealed that ICV oxytocin administration suppresses phasic dopamine neuron activity in the VTA in response to cues associated with sucrose [ 69 ]. The modulation of VTA excitatory transmission is pathway specific and may be limited to cells that express the cannabinoid receptor 1, as OT-R signaling stimulates endocannabinoid release from dopamine neurons, which acts on excitatory glutamatergic inputs to VTA neurons to suppress glutamatergic transmission [ 66 , 70 ].…”

Section: Neural Sites Of Action For Oxytocin’s Effects On Food Intakementioning

confidence: 99%

“…Additionally, reduction of sucrose consumption in rodents has also been observed when oxytocin is directly injected into the VTA or ACB core, further supporting oxytocin’s role in reward processing [ 7 , 10 ]. Indeed, a recent study from our lab has shown that lateral ICV injection of oxytocin in rats inhibits VTA dopamine neuron activity and preferentially decreases sucrose motivation and consumption over chow consumption in a choice task [ 69 ].…”

Section: Behavioral Mechanisms Mediating Central Oxytocin’s Anorexigenic Effectsmentioning

confidence: 99%

“…Further, oxytocin delivered to the cerebral ventricles, NTS, or VTA reduces motivation to work for palatable food and reduces re-instatement of food-seeking behavior [ 47 ]. As briefly mentioned above, we recently reported [ 69 ] that oxytocin reduces palatable food-seeking behavior in a conditioned place preference task, impulsive operant responding for palatable food, and motivation to work for sucrose in a free chow vs. operant sucrose choice task. These outcomes are likely mediated, in part, via action in the mesolimbic dopamine pathway as we demonstrated that ICV oxytocin reduces dopamine neuron activity in response to Pavlovian cues associated with sucrose access.…”

Section: Behavioral Mechanisms Mediating Central Oxytocin’s Anorexigenic Effectsmentioning

confidence: 99%

“…These outcomes are likely mediated, in part, via action in the mesolimbic dopamine pathway as we demonstrated that ICV oxytocin reduces dopamine neuron activity in response to Pavlovian cues associated with sucrose access. However, central oxytocin does not affect incentive learning in a procedure where sucrose motivation is increased when sucrose is consumed following an energetic motivational shift (from satiety to hunger/fasted) [ 69 ]. These data are consistent with a previous study demonstrating that instrumental incentive learning is not affected by treatment with flupenthixol, a D1 and D2 receptor antagonist [ 147 ], thereby suggesting that instrumental incentive learning is independent of dopamine signaling.…”

Section: Behavioral Mechanisms Mediating Central Oxytocin’s Anorexigenic Effectsmentioning

confidence: 99%

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Oxytocin and Food Intake Control: Neural, Behavioral, and Signaling Mechanisms

Liu

Spaulding

Rea

et al. 2021

IJMS

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The neuropeptide oxytocin is produced in the paraventricular hypothalamic nucleus and the supraoptic nucleus of the hypothalamus. In addition to its extensively studied influence on social behavior and reproductive function, central oxytocin signaling potently reduces food intake in both humans and animal models and has potential therapeutic use for obesity treatment. In this review, we highlight rodent model research that illuminates various neural, behavioral, and signaling mechanisms through which oxytocin’s anorexigenic effects occur. The research supports a framework through which oxytocin reduces food intake via amplification of within-meal physiological satiation signals rather than by altering between-meal interoceptive hunger and satiety states. We also emphasize the distributed neural sites of action for oxytocin’s effects on food intake and review evidence supporting the notion that central oxytocin is communicated throughout the brain, at least in part, through humoral-like volume transmission. Finally, we highlight mechanisms through which oxytocin interacts with various energy balance-associated neuropeptide and endocrine systems (e.g., agouti-related peptide, melanin-concentrating hormone, leptin), as well as the behavioral mechanisms through which oxytocin inhibits food intake, including effects on nutrient-specific ingestion, meal size control, food reward-motivated responses, and competing motivations.

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Section: Neural Sites Of Action For Oxytocin’s Effects On Food Intakementioning

confidence: 99%

Section: Behavioral Mechanisms Mediating Central Oxytocin’s Anorexigenic Effectsmentioning

confidence: 99%

Section: Behavioral Mechanisms Mediating Central Oxytocin’s Anorexigenic Effectsmentioning

confidence: 99%

Section: Behavioral Mechanisms Mediating Central Oxytocin’s Anorexigenic Effectsmentioning

confidence: 99%

See 2 more Smart Citations

Oxytocin and Food Intake Control: Neural, Behavioral, and Signaling Mechanisms

Liu

Spaulding

Rea

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…The OT projection from the PVN to the VTA has been implicated in the control of social behavior and feeding reward ( Mullis et al, 2013 ; Liu et al, 2020b ; Wald et al, 2020 ) (also see Klockars et al, 2015 ; Lawson et al, 2020 , for additional information on VTA OTRs in the control of food intake). Previous data from Mullis et al (2013) indicate that direct administration of OT into the VTA reduces consumption of highly palatable 10% sucrose solution.…”

Section: Source and Functions Of Oxytocinmentioning

confidence: 99%

Oxytocin as an Anti-obesity Treatment

2021

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Obesity is a growing health concern, as it increases risk for heart disease, hypertension, type 2 diabetes, cancer, COVID-19 related hospitalizations and mortality. However, current weight loss therapies are often associated with psychiatric or cardiovascular side effects or poor tolerability that limit their long-term use. The hypothalamic neuropeptide, oxytocin (OT), mediates a wide range of physiologic actions, which include reproductive behavior, formation of prosocial behaviors and control of body weight. We and others have shown that OT circumvents leptin resistance and elicits weight loss in diet-induced obese rodents and non-human primates by reducing both food intake and increasing energy expenditure (EE). Chronic intranasal OT also elicits promising effects on weight loss in obese humans. This review evaluates the potential use of OT as a therapeutic strategy to treat obesity in rodents, non-human primates, and humans, and identifies potential mechanisms that mediate this effect.

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The central oxytocinergic system of the prairie vole

Ramos,

Jiron,

Danoff

et al. 2024

Brain Struct Funct

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Oxytocin (OXT) is a peptide hormone and a neuropeptide that regulates various peripheral physiological processes and modulates behavioral responses in the central nervous system. While the humoral release occurs from the axons arriving at the median eminence, the neuropeptide is also released from oxytocinergic cell axons in various brain structures that contain its receptor, and from their dendrites in hypothalamic nuclei and potentially into the cerebrospinal fluid (CSF). Understanding oxytocin’s complex functions requires the knowledge on patterns of oxytocinergic projections in relationship to its receptor (OXTR). This study provides the first comprehensive examination of the oxytocinergic system in the prairie vole (Microtus ochrogaster), an animal exhibiting social behaviors that mirror human social behaviors linked to oxytocinergic functioning. Using light and electron microscopy, we characterized the neuroanatomy of the oxytocinergic system in this species. OXT+ cell bodies were found primarily in the hypothalamus, and axons were densest in subcortical regions. Examination of the OXT+ fibers and their relationship to oxytocin receptor transcripts (Oxtr) revealed that except for some subcortical structures, the presence of axons was not correlated with the amount of Oxtr across the brain. Of particular interest, the cerebral cortex that had high expression of Oxtr transcripts contained little to no fibers. Electron microscopy is used to quantify dense cored vesicles (DCV) in OXT+ axons and to identify potential axonal release sites. The ependymal cells that line the ventricles were frequently permissive of DCV-containing OXT+ dendrites reaching the third ventricle. Our results highlight a mechanism in which oxytocin is released directly into the ventricles and circulates throughout the ventricular system, may serve as the primary source for oxytocin that binds to OXTR in the cerebral cortex.

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Central oxytocin signaling inhibits food reward-motivated behaviors and VTA dopamine responses to food-predictive cues in male rats

Cited by 17 publications

References 86 publications

Oxytocin and Food Intake Control: Neural, Behavioral, and Signaling Mechanisms

Oxytocin and Food Intake Control: Neural, Behavioral, and Signaling Mechanisms

Oxytocin as an Anti-obesity Treatment

The central oxytocinergic system of the prairie vole

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