ReferenceID 5931
Neurochemical evidence for differential effects of acute and repeated oxytocin administration
Mol Psychiatry
A discrepancy in oxytocin's behavioral effects between acute and repeated administrations indicates distinct underlying neurobiological mechanisms. The current study employed a combination of human clinical trial and ani
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Record Fields
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- Reference Id
- 5931
- Evidence Id
- 22521
- Core Evidence Id
- 22521
- Source Reference Id
- 5125
- Herb2 Reference Id
- HBREF005922
- Subject Paper Key
- HBIN038531_30262887
- Pubmed Id
- 30262887
- Doi
- 10.1038/s41380-018-0249-4
- Paper Title
- Neurochemical evidence for differential effects of acute and repeated oxytocin administration
- Paper Abstract
- A discrepancy in oxytocin's behavioral effects between acute and repeated administrations indicates distinct underlying neurobiological mechanisms. The current study employed a combination of human clinical trial and animal study to compare neurochemical changes induced by acute and repeated oxytocin administrations. Human study analyzed medial prefrontal metabolite levels by using 1H-magnetic resonance spectroscopy, a secondary outcome in our randomized, double-blind, placebo-controlled crossover trial of 6 weeks intranasal administrations of oxytocin (48 IU/day) and placebo within-subject design in 17 psychotropic-free high-functioning men with autism spectrum disorder. Medial prefrontal transcript expression levels were analyzed in adult male C57BL/6J mice after intraperitoneal injection of oxytocin or saline either once (200 ng/100 muL/mouse, n = 12) or for 14 consecutive days (200 ng/100 muL/mouse/day, n = 16). As the results, repeated administration of oxytocin significantly decreased the medial prefrontal N-acetylaspartate (NAA; p = 0.043) and glutamate-glutamine levels (Glx; p = 0.001), unlike the acute oxytocin. The decreases were inversely and specifically associated (r = 0.680, p = 0.004 for NAA; r = 0.491, p = 0.053 for Glx) with oxytocin-induced improvements of medial prefrontal functional MRI activity during a social judgment task not with changes during placebo administrations. In wild-type mice, we found that repeated oxytocin administration reduced medial frontal transcript expression of N-methyl-D-aspartate receptor type 2B (p = 0.018), unlike the acute oxytocin, which instead changed the transcript expression associated with oxytocin (p = 0.0004) and neural activity (p = 0.0002). The present findings suggest that the unique sensitivity of the glutamatergic system to repeated oxytocin administration may explain the differential behavioral effects of oxytocin between acute and repeated administration.
- Journal
- Mol Psychiatry
- Publish Year
- 2021
- Experiment Subject
- mouse; human; men
- Experiment Type
- Clinical & Animal Experiment
- Phenotype Related
- Autism Spectrum Disorder
- Paper Title Cn
- Paper Title En
- Neurochemical evidence for differential effects of acute and repeated oxytocin administration
- Bilingual Status
- semi_complete