The effect of sertraline and 8-OH-DPAT on the PTZ_induced seizure threshold: Role of the nitrergic system

- Sertraline and 8OH-DPAT both had anticonvulsant effect.
- The effect of sertraline and 8OH-DPAT was augmented in the presence of WAY100635.
- Anticonvulsant effect of 8OH-DPAT may partly be due to interaction between 5HT1A-5HT7R.
- 5HT1A agonists such as 8OH-DPAT can lower NOx levels in brain tissue.
- Anticonvulsant effect of sertraline and 8OH-DPAT may be modulated via nitric oxide.

PurposeSerotonin is a key regulatory neurotransmitter in the CNS which plays an important role in seizure through different receptors, especially the 5HT1A subtype. The role of sertraline through the 5HT1A receptor and nitric oxide interaction on the PTZ-induced seizure threshold was investigated in this study.MethodIn this study, 70 white male mice were randomly divided into 10 groups including intact control, sham-control and eight experimental groups which received sertraline, 8-OH-DPAT, WAY100635, WAY100635 + sertraline, WAY100635 + 8-OH-DPAT, L-NAME, L-NAME + sertraline and L-NAME + 8-OH-DPAT. After 14 days of treatment in different groups, the PTZ-induced seizure threshold was assessed and the measurement of nitric oxide metabolites in the brain tissue was done with the Greiss method.ResultsThe seizure threshold was significantly increased in the sertraline and 8OH-DPAT receiving groups compared to the sham group (P < 0.001). In the presence of WAY100635, the effect of both sertraline and 8-OH-DPAT in raising the seizure threshold was more prominent (P < 0.001) but on the other hand, in the presence of L-NAME, an increase in the anticonvulsant effect of 8-OH-DPAT was observed, while L-NAME alone had no effect on the seizure threshold (P < 0.001). The NOX concentration was significantly decreased in the 8-OH-DPAT_treated group (P < 0.01), while the WAY100657 reversed it and the combination of 8-OH-DPAT with L-NAME reduced the NOX levels (P < 0.001).ConclusionsThese findings support the anticonvulsant effect of SSRIs and selective 5HT1A receptors, although serotonin receptors other than 5HT1A subtype may be involved and also it is probable that some anticonvulsant effects of the sertraline and 8-OH-DPAT are through the modulation of nitrergic system.