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 0.5mg/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 themost plausible
explanation for the proconvulsive effects of OT.

Jaar van publicatie:2012

Trefwoorden:Pentylenetetrazol, Oxytocin, Oxytocin receptor