Oxytocin Promotes Accurate Fear Discrimination and Adaptive Defensive Behaviors

Olivera-Pasilio, Valentina; Dabrowska, Joanna

doi:10.3389/fnins.2020.583878

Cited by 34 publications

(19 citation statements)

References 102 publications

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“…Conversely, systemic administration of oxytocin was shown to reduce background anxiety (noncued fear) measured in male rat FPS (Missig et al, 2010;Ayers et al, 2011). These ostensibly contrasting behavioral effects support growing evidence that oxytocin promotes fear discrimination by reducing sustained fear responses (contextual fear and noncued fear) yet strengthening fear responses to signaled, predictable, or imminent threats (Jane cek and Dabrowska, 2019; for review, see Olivera-Pasilio and Dabrowska, 2020). Indeed, recent studies investigating the BLA support the role of OTRs in facilitating accurate fear discrimination by selectively strengthening fear responses to discrete cues (CS 1 ) (Fam et al, 2018).…”

Section: Neuropeptidergic Modulators Versus Classic Neurotransmittersmentioning

confidence: 64%

Limbic Neuropeptidergic Modulators of Emotion and Their Therapeutic Potential for Anxiety and Post-Traumatic Stress Disorder

et al. 2021

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Post-traumatic stress disorder (PTSD) is characterized by hypervigilance, increased reactivity to unpredictable versus predictable threat signals, deficits in fear extinction, and an inability to discriminate between threat and safety. First-line pharmacotherapies for psychiatric disorders have limited therapeutic efficacy in PTSD. However, recent studies have advanced our understanding of the roles of several limbic neuropeptides in the regulation of defensive behaviors and in the neural processes that are disrupted in PTSD. For example, preclinical studies have shown that blockers of tachykinin pathways, such as the Tac2 pathway, attenuate fear memory consolidation in mice and thus might have unique potential as early post-trauma interventions to prevent PTSD development. Targeting this pathway might also be beneficial in regulating other symptoms of PTSD, including trauma-induced aggressive behavior. In addition, preclinical and clinical studies have shown the important role of angiotensin receptors in fear extinction and the promise of using angiotensin II receptor blockade to reduce PTSD symptom severity. Additional preclinical studies have demonstrated that the oxytocin receptors foster accurate fear discrimination by facilitating fear responses to predictable versus unpredictable threats. Complementary human imaging studies demonstrate unique neural targets of intranasal oxytocin and compare its efficacy with well-established anxiolytic treatments. Finally, promising data from human subjects have demonstrated that a selective vasopressin 1A receptor antagonist reduces anxiety induced by unpredictable threats. This review highlights these novel promising targets for the treatment of unique core elements of PTSD pathophysiology.

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Section: Neuropeptidergic Modulators Versus Classic Neurotransmittersmentioning

confidence: 64%

Limbic Neuropeptidergic Modulators of Emotion and Their Therapeutic Potential for Anxiety and Post-Traumatic Stress Disorder

et al. 2021

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“…This is in line with human studies suggesting that the effect of this neuropeptide depends on various contextual and inter-individual factors [for a review, see Bartz et al ( 4 )], and this phenomenon manifests itself also in the context-dependent influence of oxytocin on brain function ( 34 ). Results of another recent study indicate that oxytocin may serve as a warning system against potential threat cues in the environment and thus has the potential to facilitate active defensive behaviors ( 35 ). This finding contradicts the popular belief that oxytocin generally enhances social motivation and affiliative behaviors and further supports the results of human studies indicating that oxytocin can also induce antisocial effects, like aggression, envy, and distrust ( 8 , 36 ), especially in negative situations like threat or competition ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Intranasal Oxytocin Improves Social Behavior in Laboratory Beagle Dogs (Canis familiaris) Using a Custom-Made Social Test Battery

et al. 2022

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For a long time, oxytocin has been thought to have a generally positive effect on social cognition and prosocial behavior; however, recent results suggested that oxytocin has beneficial effects only under certain conditions. The aim of the present study was to explore potential associations between social competence and the effect of intranasal oxytocin on the social behavior of laboratory beagle dogs. We expected oxytocin treatment to have a more pronounced positive effect on dogs with lower baseline performance in a social test battery. Thirty-six adult dogs of both sexes received 32 IU intranasal oxytocin and physiological saline (placebo) treatment in a double-blind, cross-over design, with 17–20 days between the two sessions. Forty minutes after the treatment, dogs participated in a social test battery consisting of eight situations. The situations were carried out within one session and took 20–30 min to complete. Principal component analysis on the coded behaviors identified four components (Willingness to interact, Preference for social contact, Non-aversive response to nonsocial threat, and Non-aversive response to social threat). The subjects' behavior during the placebo condition was used to assess their baseline performance. We found that oxytocin treatment had a differential effect on the behavior depending on the baseline performance of the individuals in all components, but only two treatment × baseline performance interactions remained significant in a less sensitive analysis. In accordance with our hypothesis, oxytocin administration increased dogs' contact seeking and affiliative behaviors toward humans but only for those with low baseline performance. Dogs with low baseline performance also showed significantly more positive (friendly) reactions to social threat after oxytocin administration than after placebo, while for dogs with high baseline performance, oxytocin administration led to a more negative (fearful) reaction. These results indicate that similar to those on humans, the effects of oxytocin on dogs' social behavior are not universally positive but are constrained by individual characteristics and the context. Nevertheless, oxytocin administration has the potential to improve the social behavior of laboratory beagle dogs that are socially less proficient when interacting with humans, which could have both applied and animal welfare implications.

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“…In addition to the oxytocinergic homeostatic neurocircuitry within the hypothalamus, oxytocin neurons project to brain regions that function as key mediators of reward seeking and consumption behavior (i.e., ventral tegmental area (VTA) [ 30 ] and the nucleus accumbens (NAc)) [ 31 ] that have been implicated in the pathogenesis of obesity and drug addiction [ 32 , 33 ]. Furthermore, hypothalamic oxytocinergic neurons reach the central amygdala [ 34 , 35 ], which modulates food consumption by affecting the reward saliency of food through positive-valence mechanisms [ 36 ]. PVN oxytocinergic neurons also project to the nucleus of the solitary tract (NST) [ 37 ] in which GI vagal afferent transmissions are integrated with endocrine peripheral signals and nutrients (e.g., glucose) to process and govern energy balance [ 38 ].…”

Section: The Central Oxytocinergic System—a Framework To Understand the Role Of Oxytocin In The Coordination Of Energy Balancementioning

confidence: 99%

The Effects of Oxytocin on Appetite Regulation, Food Intake and Metabolism in Humans

Kerem

Lawson

2021

IJMS

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The hypothalamic peptide oxytocin and its receptor are involved in a range of physiological processes, including parturition, lactation, cell growth, wound healing, and social behavior. More recently, increasing evidence has established the effects of oxytocin on food intake, energy expenditure, and peripheral metabolism. In this review, we provide a comprehensive description of the central oxytocinergic system in which oxytocin acts to shape eating behavior and metabolism. Next, we discuss the peripheral beneficial effects oxytocin exerts on key metabolic organs, including suppression of visceral adipose tissue inflammation, skeletal muscle regeneration, and bone tissue mineralization. A brief summary of oxytocin actions learned from animal models is presented, showing that weight loss induced by chronic oxytocin treatment is related not only to its anorexigenic effects, but also to the resulting increase in energy expenditure and lipolysis. Following an in-depth discussion on the technical challenges related to endogenous oxytocin measurements in humans, we synthesize data related to the association between endogenous oxytocin levels, weight status, metabolic syndrome, and bone health. We then review clinical trials showing that in humans, acute oxytocin administration reduces food intake, attenuates fMRI activation of food motivation brain areas, and increases activation of self-control brain regions. Further strengthening the role of oxytocin in appetite regulation, we review conditions of hypothalamic insult and certain genetic pathologies associated with oxytocin depletion that present with hyperphagia, extreme weight gain, and poor metabolic profile. Intranasal oxytocin is currently being evaluated in human clinical trials to learn whether oxytocin-based therapeutics can be used to treat obesity and its associated sequela. At the end of this review, we address the fundamental challenges that remain in translating this line of research to clinical care.

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Oxytocin Promotes Accurate Fear Discrimination and Adaptive Defensive Behaviors

Cited by 34 publications

References 102 publications

Limbic Neuropeptidergic Modulators of Emotion and Their Therapeutic Potential for Anxiety and Post-Traumatic Stress Disorder

Limbic Neuropeptidergic Modulators of Emotion and Their Therapeutic Potential for Anxiety and Post-Traumatic Stress Disorder

Intranasal Oxytocin Improves Social Behavior in Laboratory Beagle Dogs (Canis familiaris) Using a Custom-Made Social Test Battery

The Effects of Oxytocin on Appetite Regulation, Food Intake and Metabolism in Humans

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