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Therapeutic Potential of Targeting the Oxytocinergic System

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 22850

Special Issue Editors

Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Interests: neuropsychopharmacology; oleoylethanolamide (OEA); eating disorder; brain oxytocin; gut-brain axis; pharmacological treatment; Alzheimer’s disease
Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA)–Pharmacology and Toxicology Session, University of Florence (UNIFI), 50139 Florence, Italy
Interests: neuropharmacology, animal behavior; brain histamine; brain carbonic anhydrases; oxytocin; memory; food intake stress, Azheimer's disease
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Special Issue Information

Dear Colleagues,

Oxytocin is a hypothalamic hormone that is directly secreted into the brain and reaches blood circulation through the neurohypophysis. Oxytocin modulates a wide range of neurotransmitter and neuromodulator activities as well as physiologic functions and behaviors, including social interactions, social memory response to social stimuli, decision-making, feeding behavior, emotional reactivity, aggressiveness, maternal behavior, sexual behavior, and so on. Thus, the oxytocinergic system continues to be the focus of intense exploratory research in animals and humans, as a possible therapeutic agent for the treatment of certain neuropsychiatric disorders such as autism, eating disorders, schizophrenia, and anxiety-related disorders. The potential use of oxytocin in these disorders is attracting growing interest since numerous beneficial properties are ascribed to this neuropeptide.

This Special Issue will collect evidence about oxytocin as a research tool and therapeutic agent to highlight the need for further investigations that might contribute to the development of novel, safe, and successful therapies.

Subtopics:

The oxytocin receptor system and signaling

Different populations of oxytocin neurons: magnocellular and parvocellular oxytocin neurons

Central versus peripheral oxytocin system

Oxytocin in neuropsychiatric disorders

Oxytocin and addiction

Oxytocin and autism

Oxytocin and control of eating and energy metabolism

Oxytocin and sexual behavior

Oxytocin and stress and aggressiveness

Dr. Adele Romano
Dr. Gustavo Provens
Guest Editors

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Keywords

  • oxytocin
  • oxytocin receptor
  • magnocellular
  • parvocellular
  • anxiety
  • autism
  • eating disorders
  • mood disorders
  • neuropsychiatric disorders
  • sexual behavior
  • maternal behavior
  • eating behavior
  • stress
  • successful therapies

Published Papers (7 papers)

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Editorial

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4 pages, 454 KiB  
Editorial
Therapeutic Potential of Targeting the Oxytocinergic System
by Adele Romano and Gustavo Provensi
Int. J. Mol. Sci. 2022, 23(21), 13295; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113295 - 31 Oct 2022
Viewed by 1074
Abstract
The nine amino acid neuropeptide oxytocin (OXT, Cys–Tyr–Ile–Gln–Asn–Cys–Pro–Leu–Gly–NH2) is one of the most studied hormones of the body [...] Full article
(This article belongs to the Special Issue Therapeutic Potential of Targeting the Oxytocinergic System)
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Research

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10 pages, 1612 KiB  
Article
Sex Differences in the Hypothalamic Oxytocin Pathway to Locus Coeruleus and Augmented Attention with Chemogenetic Activation of Hypothalamic Oxytocin Neurons
by Xin Wang, Joan B. Escobar and David Mendelowitz
Int. J. Mol. Sci. 2021, 22(16), 8510; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168510 - 07 Aug 2021
Cited by 9 | Viewed by 2269
Abstract
The tightly localized noradrenergic neurons (NA) in the locus coeruleus (LC) are well recognized as essential for focused arousal and novelty-oriented responses, while many children with autism spectrum disorder (ASD) exhibit diminished attention, engagement and orienting to exogenous stimuli. This has led to [...] Read more.
The tightly localized noradrenergic neurons (NA) in the locus coeruleus (LC) are well recognized as essential for focused arousal and novelty-oriented responses, while many children with autism spectrum disorder (ASD) exhibit diminished attention, engagement and orienting to exogenous stimuli. This has led to the hypothesis that atypical LC activity may be involved in ASD. Oxytocin (OXT) neurons and receptors are known to play an important role in social behavior, pair bonding and cognitive processes and are under investigation as a potential treatment for ASD. However, little is known about the neurotransmission from hypothalamic paraventricular (PVN) OXT neurons to LC NA neurons. In this study, we test, in male and female rats, whether PVN OXT neurons excite LC neurons, whether oxytocin is released and involved in this neurotransmission, and whether activation of PVN OXT neurons alters novel object recognition. Using “oxytocin sniffer cells” (CHO cells that express the human oxytocin receptor and a Ca indicator) we show that there is release of OXT from hypothalamic PVN OXT fibers in the LC. Optogenetic excitation of PVN OXT fibers excites LC NA neurons by co-release of OXT and glutamate, and this neurotransmission is greater in males than females. In male, but not in female animals, chemogenetic activation of PVN OXT neurons increases attention to novel objects. Full article
(This article belongs to the Special Issue Therapeutic Potential of Targeting the Oxytocinergic System)
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34 pages, 5889 KiB  
Article
Aberrant Early in Life Stimulation of the Stress-Response System Affects Emotional Contagion and Oxytocin Regulation in Adult Male Mice
by Giovanni Laviola, Ludovica Maria Busdraghi, Noemi Meschino, Carla Petrella and Marco Fiore
Int. J. Mol. Sci. 2021, 22(9), 5039; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22095039 - 10 May 2021
Cited by 11 | Viewed by 2889
Abstract
Results over the last decades have provided evidence suggesting that HPA axis dysfunction is a major risk factor predisposing to the development of psychopathological behaviour. This susceptibility can be programmed during developmental windows of marked neuroplasticity, allowing early-life adversity to convey vulnerability to [...] Read more.
Results over the last decades have provided evidence suggesting that HPA axis dysfunction is a major risk factor predisposing to the development of psychopathological behaviour. This susceptibility can be programmed during developmental windows of marked neuroplasticity, allowing early-life adversity to convey vulnerability to mental illness later in life. Besides genetic predisposition, also environmental factors play a pivotal role in this process, through embodiment of the mother’s emotions, or via nutrients and hormones transferred through the placenta and the maternal milk. The aim of the current translational study was to mimic a severe stress condition by exposing female CD-1 mouse dams to abnormal levels of corticosterone (80 µg/mL) in the drinking water either during the last week of pregnancy (PreCORT) or the first one of lactation (PostCORT), compared to an Animal Facility Rearing (AFR) control group. When tested as adults, male mice from PostCORT offspring and somewhat less the PreCORT mice exhibited a markedly increased corticosterone response to acute restraint stress, compared to perinatal AFR controls. Aberrant persistence of adolescence-typical increased interest towards novel social stimuli and somewhat deficient emotional contagion also characterised profiles in both perinatal-CORT groups. Intranasal oxytocin (0 or 20.0 µg/kg) generally managed to reduce the stress response and restore a regular behavioural phenotype. Alterations in density of glucocorticoid and mineralocorticoid receptors, oxytocin and µ- and κ-opioid receptors were found. Changes differed as a function of brain areas and the specific age window of perinatal aberrant stimulation of the HPA axis. Present results provided experimental evidence in a translational mouse model that precocious adversity represents a risk factor predisposing to the development of psychopathological behaviour. Full article
(This article belongs to the Special Issue Therapeutic Potential of Targeting the Oxytocinergic System)
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Review

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23 pages, 413 KiB  
Review
Targeting the Oxytocinergic System: A Possible Pharmacological Strategy for the Treatment of Inflammation Occurring in Different Chronic Diseases
by Marzia Friuli, Barbara Eramo, Marta Valenza, Caterina Scuderi, Gustavo Provensi and Adele Romano
Int. J. Mol. Sci. 2021, 22(19), 10250; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910250 - 23 Sep 2021
Cited by 13 | Viewed by 2581
Abstract
Unresolved inflammation represents a central feature of different human pathologies including neuropsychiatric, cardiovascular, and metabolic diseases. The epidemiologic relevance of such disorders justifies the increasing interest in further understanding the mechanisms underpinning the inflammatory process occurring in such chronic diseases to provide potential [...] Read more.
Unresolved inflammation represents a central feature of different human pathologies including neuropsychiatric, cardiovascular, and metabolic diseases. The epidemiologic relevance of such disorders justifies the increasing interest in further understanding the mechanisms underpinning the inflammatory process occurring in such chronic diseases to provide potential novel pharmacological approaches. The most common and effective therapies for controlling inflammation are glucocorticoids; however, a variety of other molecules have been demonstrated to have an anti-inflammatory potential, including neuropeptides. In recent years, the oxytocinergic system has seen an explosion of scientific studies, demonstrating its potential to contribute to a variety of physiological processes including inflammation. Therefore, the aim of the present review was to understand the role of oxytocin in the modulation of inflammation occurring in different chronic diseases. The criterion we used to select the diseases was based on the emerging literature showing a putative involvement of the oxytocinergic system in inflammatory processes in a variety of pathologies including neurological, gastrointestinal and cardiovascular disorders, diabetes and obesity. The evidence reviewed here supports a beneficial role of oxytocin in the control of both peripheral and central inflammatory response happening in the aforementioned pathologies. Although future studies are necessary to elucidate the mechanistic details underlying such regulation, this review supports the idea that the modulation of the endogenous oxytocinergic system might represent a new potential pharmacological approach for the treatment of inflammation. Full article
(This article belongs to the Special Issue Therapeutic Potential of Targeting the Oxytocinergic System)
27 pages, 446 KiB  
Review
Oxytocin and Fear Memory Extinction: Possible Implications for the Therapy of Fear Disorders?
by Elisabetta Baldi, Alessia Costa, Barbara Rani, Maria Beatrice Passani, Patrizio Blandina, Adele Romano and Gustavo Provensi
Int. J. Mol. Sci. 2021, 22(18), 10000; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810000 - 16 Sep 2021
Cited by 9 | Viewed by 3765
Abstract
Several psychiatric conditions such as phobias, generalized anxiety, and post-traumatic stress disorder (PTSD) are characterized by pathological fear and anxiety. The main therapeutic approach used in the management of these disorders is exposure-based therapy, which is conceptually based upon fear extinction with the [...] Read more.
Several psychiatric conditions such as phobias, generalized anxiety, and post-traumatic stress disorder (PTSD) are characterized by pathological fear and anxiety. The main therapeutic approach used in the management of these disorders is exposure-based therapy, which is conceptually based upon fear extinction with the formation of a new safe memory association, allowing the reduction in behavioral conditioned fear responses. Nevertheless, this approach is only partially resolutive, since many patients have difficulty following the demanding and long process, and relapses are frequently observed over time. One strategy to improve the efficacy of the cognitive therapy is the combination with pharmacological agents. Therefore, the identification of compounds able to strengthen the formation and persistence of the inhibitory associations is a key goal. Recently, growing interest has been aroused by the neuropeptide oxytocin (OXT), which has been shown to have anxiolytic effects. Furthermore, OXT receptors and binding sites have been found in the critical brain structures involved in fear extinction. In this review, the recent literature addressing the complex effects of OXT on fear extinction at preclinical and clinical levels is discussed. These studies suggest that the OXT roles in fear behavior are due to its local effects in several brain regions, most notably, distinct amygdaloid regions. Full article
(This article belongs to the Special Issue Therapeutic Potential of Targeting the Oxytocinergic System)
18 pages, 629 KiB  
Review
Oxytocin and Addiction: Potential Glutamatergic Mechanisms
by Megana Sundar, Devon Patel, Zachary Young and Kah-Chung Leong
Int. J. Mol. Sci. 2021, 22(5), 2405; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052405 - 27 Feb 2021
Cited by 17 | Viewed by 4952
Abstract
Recently, oxytocin (OXT) has been investigated for its potential therapeutic role in addiction. OXT has been found to diminish various drug-seeking and drug-induced behaviors. Although its behavioral effects are well-established, there is not much consensus on how this neuropeptide exerts its effects. Previous [...] Read more.
Recently, oxytocin (OXT) has been investigated for its potential therapeutic role in addiction. OXT has been found to diminish various drug-seeking and drug-induced behaviors. Although its behavioral effects are well-established, there is not much consensus on how this neuropeptide exerts its effects. Previous research has given thought to how dopamine (DA) may be involved in oxytocinergic mechanisms, but there has not been as strong of a focus on the role that glutamate (Glu) has. The glutamatergic system is critical for the processing of rewards and the disruption of glutamatergic projections produces the behaviors seen in drug addicts. We introduce the idea that OXT has direct effects on Glu transmission within the reward processing pathway. Thus, OXT may reduce addictive behaviors by restoring abnormal drug-induced changes in the glutamatergic system and in its interactions with other neurotransmitters. This review offers insight into the mechanisms through which a potentially viable therapeutic target, OXT, could be used to reduce addiction-related behaviors. Full article
(This article belongs to the Special Issue Therapeutic Potential of Targeting the Oxytocinergic System)
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21 pages, 1255 KiB  
Review
Oxytocin Signaling as a Target to Block Social Defeat-Induced Increases in Drug Abuse Reward
by Carmen Ferrer-Pérez, Marina D. Reguilón, José Miñarro and Marta Rodríguez-Arias
Int. J. Mol. Sci. 2021, 22(5), 2372; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052372 - 27 Feb 2021
Cited by 10 | Viewed by 4397
Abstract
There is huge scientific interest in the neuropeptide oxytocin (OXT) due to its putative capacity to modulate a wide spectrum of physiological and cognitive processes including motivation, learning, emotion, and the stress response. The present review seeks to increase the understanding of the [...] Read more.
There is huge scientific interest in the neuropeptide oxytocin (OXT) due to its putative capacity to modulate a wide spectrum of physiological and cognitive processes including motivation, learning, emotion, and the stress response. The present review seeks to increase the understanding of the role of OXT in an individual’s vulnerability or resilience with regard to developing a substance use disorder. It places specific attention on the role of social stress as a risk factor of addiction, and explores the hypothesis that OXT constitutes a homeostatic response to stress that buffers against its negative impact. For this purpose, the review summarizes preclinical and clinical literature regarding the effects of OXT in different stages of the addiction cycle. The current literature affirms that a well-functioning oxytocinergic system has protective effects such as the modulation of the initial response to drugs of abuse, the attenuation of the development of dependence, the blunting of drug reinstatement and a general anti-stress effect. However, this system is dysregulated if there is continuous drug use or chronic exposure to stress. In this context, OXT is emerging as a promising pharmacotherapy to restore its natural beneficial effects in the organism and to help rebalance the functions of the addicted brain. Full article
(This article belongs to the Special Issue Therapeutic Potential of Targeting the Oxytocinergic System)
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