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

Seizure. 2017 Feb:45:119-124. doi: 10.1016/j.seizure.2016.12.005. Epub 2016 Dec 15.

Abstract

Purpose: Serotonin 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.

Method: In 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 14days 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.

Results: The 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).

Conclusions: These 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.

Keywords: 5HT(1A) receptor; L-NAME; Nitric oxide; Pentylenetetrazole; Seizure; Sertraline.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / toxicity*
  • Analysis of Variance
  • Animals
  • Convulsants / toxicity*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • NG-Nitroarginine Methyl Ester / therapeutic use
  • Nitric Oxide / metabolism*
  • Pentylenetetrazole / toxicity*
  • Piperazines / therapeutic use
  • Pyridines / therapeutic use
  • Seizures* / chemically induced
  • Seizures* / drug therapy
  • Seizures* / metabolism
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Serotonin Antagonists / therapeutic use
  • Sertraline / therapeutic use*

Substances

  • Convulsants
  • Piperazines
  • Pyridines
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Nitric Oxide
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Sertraline
  • NG-Nitroarginine Methyl Ester
  • Pentylenetetrazole