Posterior hypothalamus glutamate infusion decreases pentylenetetrazol-induced seizures of male rats through hippocampal histamine increase

- Glutamate infusion into posterior hypothalamus prevented convulsions.
- Blocking OX2Rs increased seizure duration, but not the seizure stage.
- Blocking GluRs and OX2Rs reversed the glutamate effect on the stages and duration.
- Glutamate increased hippocampal histamine, which was reverted by AMPA antagonism.
- Seizure control by glutamate application may be due to the histamine build-up.

ObjectivesSeizures are epileptic manifestations that are intrinsically modulated through different neurotransmitters and receptor systems. Although glutamate increases excitation and hence seizures, it activates other systems which could potentially terminate seizures. Histamine originates from neurons of the posterior hypothalamus (PH) and can mediate anticonvulsant properties, but the effect of local PH glutamate on hippocampal histamine content is unknown. Therefore, in this study, the effect of PH glutamate and the involvement of hippocampal histamine in pentylenetetrazol (PTZ) induced seizure activity was studied.Materials and methodsOX2R antagonist (TCS OX2 29, 40 nmol/1 μl, intra-PH), AMPA/Kainate receptor antagonist (CNQX, 3 mM, intra-PH) and glutamate (1 mM) were injected bilaterally into PH using stereotaxic surgery. The intravenous PTZ infusion model was used to generate behavioral convulsions and the amount of hippocampal histamine content was then measured using a biochemical method.ResultsAdministration of glutamate into PH decreased both seizure stage and the duration of tonic-clonic convulsion (TCC) with increasing TCC latency and hippocampal histamine content. Blocking OX2Rs alone or coinhibition of OX2Rs and AMPA/kainate receptors reversed these effects by increasing both seizure stage and TCC duration, and by decreasing both latency and consequent histamine content.ConclusionsOur findings suggest that glutamate administration into PH may control seizures (stages and duration) through increasing the hippocampal histamine content.