Proconvulsive effects of oxytocin in the generalized pentylenetetrazol mouse model are mediated by vasopressin 1a receptors
Abstract
The possible involvement of oxytocin (OT) in the generation of seizures has not received a lot of attention in the past, although generalized epileptic convulsions were observed in humans following intravenous OT infusion. We here aimed to investigate the effect of exogenous OT administration on seizure susceptibility in C57Bl/6 mice subjected to the pentylenetetrazol (PTZ) model. In addition, we studied via which receptor possible effects on seizure thresholds could be mediated since OT binds to both the OT receptor (OTR) and the vasopressin 1a receptor (V1aR). We showed that C57Bl/6 mice treated with 0.5 mg/kg OT had decreased PTZ thresholds for ear twitch, myoclonic twitch, tail twitch, forelimb clonus and falling. This pronconvulsive effect was reversed by the OTR antagonist L-368.899, however, it was not mimicked by the OTR agonist carbetocin (CBT). Nevertheless, CBT had antidepressant-like effects in the forced swim test that could be reversed by L-368.899. These experiments shed some doubt on the involvement of OTR in the observed effect of OT on seizure thresholds. Therefore, we investigated the role of the V1aR as a possible mediator of the proconvulsive effects of OT. We found that the proconvulsive effects of both arginine vasopressin and OT were reversed by the V1aR antagonist SR49059. In summary, OT has proconvulsive effects in our mouse model of generalized seizures that could not be mimicked by CBT. Our results suggest that the binding of OT to V1aRs is the most plausible explanation for the proconvulsive effects of OT.
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Peripherally administered OT and AVP produce similar effects in reducing heart rate and body temperature, inducing contractions in ejaculatory tissues, and promoting seizure susceptibility in male rats and rabbits.
“Peripherally administered OT and AVP produce similar effects in reducing heart rate and body temperature, inducing contractions in ejaculatory tissues, and in promoting seizure susceptibility in male rats and rabbits [37; 38; 39].”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [38]
These effects of OT and AVP can be inhibited by selective V1aR antagonists but not by OTR antagonists.
“These effects of OT and AVP can be inhibited by selective V1aR but not OTR antagonists.”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [38]
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Agonist selectivity in the oxytocin/vasopressin receptor family: new insights and challenges
Chini, B., & Manning, M. (2007) · Biochemical Society Transactions · doi:10.1042/bst0350737 · Cited by 123 · see citing works
Schorscher-Petcu, A., Dupré, A., & Tribollet, E. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.06.016 · Cited by 111 · see citing works
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Song, Z., & Albers, H. E. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.10.004 · Cited by 244 · see citing works
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Neuropeptide diversity and the regulation of social behavior in New World primates
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- Authors
- Loyens, E., Vermoesen, K., Schallier, A., Michotte, Y., & Smolders, I.
- Affiliations
- Vrije Universiteit Brussel (BE)
- Corresponding author
- Smolders, I.
- ORCID
- Smolders, I.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 1436
- Pages
- 43-50
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2070020820
- Cited by
- 25
- References
- 3
- Citations by year
- 2026: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 5 · 2015: 1 · 2014: 4 · 2013: 2 · 2012: 3
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Queen Elisabeth Medical Foundation
- FWO-Vlaanderen (G.0163.10N)
- Vrije Universiteit Brussel (GOA61)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, vasopressin 1a receptor, pentylenetetrazole, generalized seizures, seizure susceptibility, oxytocin receptor, vasopressin, carbetocin, L-368,899, antidepressant-like effects, forced swim test, C57BL/6 mice
- MeSH terms
- Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Mice, Inbred C57BL, Oxytocin, Pentylenetetrazole, Seizures, Receptors, Vasopressin, Mice
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