The Complex Role of Oxytocin in Fear Acquisition and Generalization

Psychoneuroendocrinology, Journal Year: 2025, Volume and Issue: 176, P. 107421 - 107421

Published: March 5, 2025

Language: Английский

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The Role of Oxytocin Neurons in the Paraventricular Nucleus in Chronic-Sleep-Deprivation-Mediated Abnormal Cardiovascular Responses

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(4), P. 220 - 220

Published: March 25, 2025

Sleep disorders increase the risk of cardiovascular diseases. However, underlying mechanisms remain unclear. This study aims to examine critical role oxytocin neurons in paraventricular nucleus (PVNOXT) regulating system and elucidate potential through which sleep disturbance may contribute In this study, using an automated deprivation system, mice were given chronic (cSD) for 7 days, 6 h per day. cSD induced blood transcriptomic alterations accompanied by lower heart rate, higher pressure, elevated cardiac autophagy/apoptosis. Instant optogenetic activation provoked rate suppression normal mice, whereas precipitated intermittent arrest. On contrary, inhibition PVNOXT showed no influence on but it attenuated cSD-induced rise pressure. Long-term low-frequency stimulation (LTF) decreased neuronal excitability release, effectively reversing cSD-mediated responses. Mechanistically, triggered upregulation blood-derived 3-mercaptopyruvate sulfurtransferase (mPST), a postsynaptic activity certain extent. The quick long-term decrease LTF could lead feedback mPST expression thus reverse Altogether, modulation mediate abnormalities without affecting mice. Our research provided targets key diseases associated with disorders.

Language: Английский

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Oxytocin and autism: Insights from clinical trials and animal models

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 92, P. 103015 - 103015

Published: March 30, 2025

Language: Английский

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Enhanced disgust generalization in obsessive–compulsive disorder is related to insula and putamen hyperactivity

Psychological Medicine, Journal Year: 2025, Volume and Issue: 55

Published: Jan. 1, 2025

Abstract Background Compulsive cleaning is a characteristic symptom of particular subtype obsessive–compulsive disorder (OCD) and often accompanied by intense disgust. While overgeneralization threat key factor in the development symptoms, previous studies have primarily focused on fear generalization rarely examined disgust generalization. A systematic determination behavioral neural mechanisms underlying individuals with contamination concern crucial for enhancing our understanding OCD. Method In this study, we recruited 27 high concerns 30 low concerns. Both groups performed task while undergoing functional magnetic resonance imaging (fMRI). Results The results revealed that had higher expectancy scores stimulus GS4 (the most similar to CS+) exhibited levels activation left insula putamen. Moreover, putamen were positively correlated questionnaire core ratings also rating CS+ during stage. Conclusion Hyperactivation neutrally mediates degree subclinical OCD individuals. This study indicates altered plays an important role provides evidence involved. These insights may serve as basis further exploration pathogenesis future.

Language: Английский

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Intranasal oxytocin as a treatment for anxiety and autism: From subclinical to clinical applications

Peptides, Journal Year: 2024, Volume and Issue: 176, P. 171211 - 171211

Published: April 4, 2024

Language: Английский

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Integrative analysis prioritised oxytocin-related biomarkers associated with the aetiology of autism spectrum disorder

EBioMedicine, Journal Year: 2022, Volume and Issue: 81, P. 104091 - 104091

Published: June 2, 2022

Autism spectrum disorder (ASD) is a neurodevelopmental with high phenotypic and genetic heterogeneity. The common variants of specific oxytocin-related genes (OTRGs), particularly OXTR, are associated the aetiology ASD. contribution rare variations in OTRGs to ASD remains unclear.We catalogued publicly available de novo mutations (DNMs) [from 6,511 patients 3,391 controls], inherited (RIVs) 1,786 both copy number (dnCNVs) CNVs (ihCNVs) 15,581 6,017 controls] 963 curated explore their pathology, respectively. Finally, combined model was designed prioritise each gene by integrating DNMs CNVs.The were significantly aetiology, order dnCNVs > ihCNVs DNMs. Furthermore, 172 connected 286 core prioritised positively contribute including top-ranked MAPK3. Probands carrying disruptive these estimated account for 10∼11% all probands.Our findings suggest that may be potential biomarkers predicting effects oxytocin treatment.Guangdong Key Project, National Natural Science Foundation China, Laboratory Clinical Diagnosis Translational Research Zhejiang Province.

Language: Английский

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The Angiotensin Antagonist Losartan Modulates Social Reward Motivation and Punishment Sensitivity via Modulating Midbrain-Striato-Frontal Circuits

Journal of Neuroscience, Journal Year: 2022, Volume and Issue: 43(3), P. 472 - 483

Published: Dec. 6, 2022

Social deficits and dysregulations in dopaminergic midbrain-striato-frontal circuits represent transdiagnostic symptoms across psychiatric disorders. Animal models suggest that interactions between the dopamine (DA) renin-angiotensin system (RAS) may modulate learning reward-related processes. The present study therefore examined behavioral neural effects of Angiotensin II type 1 receptor (AT1R) antagonist losartan on social reward punishment processing humans. A preregistered randomized double-blind placebo-controlled between-subject pharmacological design was combined with a incentive delay (SID) functional MRI (fMRI) paradigm during which subjects could avoid or gain reward. Healthy volunteers received single-dose (50 mg, n = 43, female 17) placebo ( 44, 20). We evaluated reaction times (RTs) emotional ratings as activation connectivity outcomes. Relative to placebo, modulated time arousal differences On level losartan-enhanced motivational salience rewards accompanied by stronger ventral striatum-prefrontal anticipation. Losartan increased reward-neutral difference tegmental area (VTA) attenuated VTA associated bilateral insula response outcome phase. Thus, approach-avoidance motivation versus via modulating distinct core nodes circuits. findings document modulatory role these processes, suggesting promising treatment target alleviate dysregulations. SIGNIFICANCE STATEMENT anhedonia characterize several mental disorders have been linked brain. Based initial from animal we here combine blockade demonstrate AT1R enhances attenuates negative impact communication for first an important humans render novel

Language: Английский

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Exaggerated sensitivity to threat and reduced medial prefrontal engagement during threat generalization in reactive aggressive adolescents

NeuroImage, Journal Year: 2024, Volume and Issue: 294, P. 120645 - 120645

Published: May 10, 2024

Aggressive adolescents tend to exhibit abnormal fear acquisition and extinction, reactive aggressive are often more anxious. However, the relationship between generalization aggression (RA) remains unknown. According Reactive-Proactive Aggression Questionnaire (RPQ) scores, 61 were divided into two groups, namely, a high RA group (N = 30) low (LA) 31). All participants underwent three consecutive phases of Pavlovian conditioning paradigm (i.e., habituation, acquisition, generalization), neural activation medial prefrontal cortex (mPFC) was assessed by functional near-infrared spectroscopy (fNIRS). The stimuli ten circles with varying sizes, including conditioned (CSs) eight (GSs). A scream at 85 dB served as auditory unconditioned stimulus (US). US expectancy ratings both CSs GSs higher in than LA group. fNIRS results showed that evoked lower mPFC compared during generalization. These findings suggest abnormalities prototypical dysregulations RA. They provide neurocognitive evidence for dysregulated learning mechanisms underlying RA, highlighting need develop emotional regulation interventions these individuals.

Language: Английский

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Is the efficacy of oxytocin for autism diminished at higher dosages or repeated doses?: Potential mechanisms and candidate solutions

Peptides, Journal Year: 2023, Volume and Issue: 171, P. 171133 - 171133

Published: Dec. 9, 2023

Language: Английский

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Oxytocin Attenuates Yohimbine-Induced Reinstatement of Alcohol-Seeking in Female Rats via the Central Amygdala

Behavioral Sciences, Journal Year: 2023, Volume and Issue: 13(7), P. 556 - 556

Published: July 4, 2023

Alcohol use disorder is a significant public health concern, further exacerbated by an increased risk of relapse due to stress. In addition, factors such as biological sex may contribute the progression addiction, females are especially susceptible stress-induced relapse. While there have been many studies surrounding potential pharmacological interventions for male ethanol reinstatement, research regarding scarce. Recently, neuropeptide oxytocin has gained interest possible intervention The present study examines how affects yohimbine-induced reinstatement ethanol-seeking in female rats using self-administration paradigm. Adult were trained press lever access daily sessions. Rats then underwent extinction training before test. administered with yohimbine demonstrated significantly higher response indicating behavior. Oxytocin administration, both systemically and directly into central amygdala, attenuated effect findings from this establish that effective at attenuating alcohol-relapse behavior mediated stressor modulated amygdala females. This provides valuable insight oxytocin's therapeutic alcohol

Language: Английский

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