Adolescent exposure to oxytocin, but not the selective oxytocin receptor agonist TGOT, increases social behavior and plasma oxytocin in adulthood
Abstract
There are indications that exposing adolescent rodents to oxytocin (OT) may have positive "trait-changing" effects resulting in increased sociability and decreased anxiety that last well beyond acute drug exposure and into adulthood. Such findings may have relevance to the utility of OT in producing sustained beneficial effects in human psychiatric conditions. The present study further examined these effects using an intermittent regime of OT exposure in adolescence, and using Long Evans rats, that are generally more sensitive to the acute prosocial effects of OT. As OT has substantial affinity for the vasopressin V1a receptor (V1aR) in addition to the oxytocin receptor (OTR), we examined whether a more selective peptidergic OTR agonist - [Thr4, Gly7]-oxytocin (TGOT) - would have similar lasting effects on behavior. Male Long Evans rats received OT or TGOT (0.5-1mg/kg, intraperitoneal), once every three days, for a total of 10 doses during adolescence (postnatal day (PND) 28-55). Social and anxiety-related behaviors were assessed during acute administration as well as later in adulthood (from PND 70 onwards). OT produced greater acute behavioral effects than TGOT, including an inhibition of social play and reduced rearing, most likely reflecting primary sedative effects. In adulthood, OT but not TGOT pretreated rats displayed lasting increases in social interaction, accompanied by an enduring increase in plasma OT. These findings confirm lasting behavioral and neuroendocrine effects of adolescent OT exposure. However, the absence of such effects with TGOT suggests possible involvement of the V1aR as well as the OTR in this example of developmental neuroplasticity.
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One paper concluded that adolescent oxytocin exposure increases plasma oxytocin in adulthood, but its extracted samples showed no group differences; the authors built their interpretation on unextracted plasma measurements.
“One of those papers concludes that adolescent exposure to oxytocin increases plasma oxytocin in adulthood, and it might be expected that this conclusion was drawn from data on extracted plasma (70).Not so: the data from extracted samples showed no differences between groups: instead, the authors built their interpretation on the measurements of unextracted plasma.”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [70]
Three studies that compared ELISA oxytocin measurements of the same samples with and without extraction all found no correlations.
“Three studies have compared ELISA oxytocin measurements of the same samples with and without extraction (69-71): all reported no correlations.”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [70]
Male rats given oxytocin injections every 3 days from postnatal day 28 to 55 spent more time in close proximity to conspecifics than control animals when tested at postnatal day 70.
“When tested in a social interaction test at PND70, their behavior appeared similar to what was described above, with their spending more time in close proximity to conspecifics than control animals (42).”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [42]
Peripubertal oxytocin administration increases oxytocin receptor mRNA expression in the hypothalamus and plasma oxytocin levels in adult male rats.
“Similar to what was discussed in terms of behavioral effects, there does appear to be a “critical period” of organization that extends into peripubertal development, with peripubertal Oxt administration increasing Oxtr mRNA expression in the hypothalamus (41) and plasma Oxt levels (42) in adult male rats.”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [42]
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References 55 · Cited by 35
- Authors
- Suraev, A. S., Bowen, M. T., Ali, S. O., Hicks, C., Ramos, L., & McGregor, I. S.
- Affiliations
- The University of Sydney (AU)
- Corresponding author
- McGregor, Iain S.
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 65
- Issue
- 5
- Pages
- 488-496
- ISSN
- 0018-506X (ISSN-L)
- OpenAlex
- W2046372653
- Cited by
- 35
- References
- 55
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 9 · 2014: 3
- FWCI
- 9.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council
- Australian Research Council
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- oxytocin, adolescent exposure, oxytocin receptor agonists, vasopressin V1a receptor, social behavior, anxiety, plasma oxytocin, developmental neuroplasticity, Long-Evans rats, social interaction, sedative effects, social play
- MeSH terms
- Animals, Anxiety, Arginine Vasopressin, Corticosterone, Male, Oxytocin, Play and Playthings, Social Behavior, Up-Regulation, Receptors, Oxytocin, Rats, Long-Evans, Rats
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