Anxiolytic Activity of Pioglitazone in Rat Pups Exposed to Febrile Seizure

Background:Anxiety is a negative emotional response associated with the perception of ambiguous stimuli. Anxiety enhances seizure frequency and epileptic seizures also showed anxiogenic effects. Early life febrile seizures (FS) enhanced anxiety behaviors. Previous studies showed that targeting peroxisome proliferator-activated receptor gamma (PPAR-γ) offered novel strategies as an anxiolytic system. Researches emphasized that PPAR-γ has the ability to modulate anxiety-related behaviors. On the other hand, activation of PPAR-γ, by pioglitazone (PGZ, an PPAR-γ agonist), reduced inflammation and exerted anxiolytic effect in some patients. As seizures also can induce inflammatory processes, the aim of this study was the evaluation of pioglitazone effect on anxiety behaviors of rat pups undergone chemical febrile seizures. Methods:Male wistar rat pups were divided into four groups (n=10 in each group). In all groups, febrile seizures were induced by LPS injection (200 μg/kg, i.p.) and 2.5 hr. later, sub-convulsive dose of kainic acid (1.75 mg/kg, i.p.) was injected. These injections were repeated for 3 days (P7, P12 and P17). Rat pups of control group were treated with normal saline (NS), i.p. for 8 days (P8-P11 and P13-P17). In experimental groups pups were treated with three different doses of PGZ (5, 10, and 20 mg/kg, i.p.) in similar schedule with control. At the end of experimental protocol, the elevated-plus maze (EPM) test was done. Results:According to recorded behaviors in EPM, results showed significant effect of PGZ on anxiety behaviors (open arm entries (%), open arm times (%), and total arm entries compared to Control group. The higher dose of PGZ showed more effective. Conclusion: The present results indicated that pioglitazone had ameliorative effects on anxiety-related behaviors induced by febrile seizure in rat pups probably acting as an agonist of PPAR-γ receptors. Such an effect of PGZ could be related to anti-inflammatory functions of PPAR-γ systems.

Keywords:

Pioglitazone , PPAR-γ , Febrile seizure , Anxiety