Proconvulsive effects of oxytocin in the generalized pentylenetetrazol mouse model are mediated by vasopressin 1a receptors.
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.
Department of Pharmaceutical Chemistry and Drug Analysis, CePhar, Center for Neuroscience, Vrije Universtiteit Brussel, Laarbeeklaan 103, 1090 Brussel, Belgium. eloyens@vub.ac.be
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E
Loyens
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Vermoesen
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A
Schallier
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Y
Michotte
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Smolders
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008810:Mice, Inbred C57BL; D010121:Oxytocin / Q000008:administration & dosage*; D010433:Pentylenetetrazole; D017483:Receptors, Vasopressin / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D017483:Receptors, Vasopressin; D010121:Oxytocin; D010433:Pentylenetetrazole