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. 2018 Aug 13;19(1):49.
doi: 10.1186/s12868-018-0445-9.

The effect of intracerebroventricular administration of orexin receptor type 2 antagonist on pentylenetetrazol-induced kindled seizures and anxiety in rats

Saeedeh Asadi  1 , Ali Roohbakhsh  2 , Ali Shamsizadeh  3 , Masoud Fereidoni  1 , Elham Kordijaz  1 , Ali Moghimi  4
Affiliations

The effect of intracerebroventricular administration of orexin receptor type 2 antagonist on pentylenetetrazol-induced kindled seizures and anxiety in rats

Saeedeh Asadi et al. BMC Neurosci. .

Abstract

Background: Current antiepileptic drugs are not able to prevent recurrent seizures in all patients. Orexins are excitatory hypothalamic neuropeptides that their receptors (Orx1R and Orx2R) are found almost in all major regions of the brain. Pentylenetetrazol (PTZ)-induced kindling is a known experimental model for epileptic seizures. The purpose of this study was to evaluate the effect of Orx2 receptor antagonist (TCS OX2 29) on seizures and anxiety of PTZ-kindled rats.

Results: Our results revealed that similar to valproate, administration of 7 µg/rat of TCS OX2 29 increased the latency period and decreased the duration time of 3rd and 4th stages of epileptiform seizures. Besides, it significantly decreased mean of seizure scores. However, TCS OX2 29 did not modulate anxiety induced by repeated PTZ administration.

Conclusion: This study showed that blockade of Orx2 receptor reduced seizure-related behaviors without any significant effect on PTZ-induced anxiety.

Keywords: Anxiety; Kindling; Orexin; Orx2 receptor; PTZ; Seizure.

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Figures

Fig. 1
Fig. 1
The effect of intracerebroventricular injection of TCS OX2 29 (1, 3.5 and 7 μg/rat) and valproate (26 µg/rat) on median of seizure scores in pentylenetetrazol-kindled rats. TCS OX2 29 at the dose of 7 μg/rat reduced median of seizure scores. Each bar represents median ± interquartiles. **P < 0.01 compared to vehicle-treated rats. In each group n = 7
Fig. 2
Fig. 2
The effect of intracerebroventricular injection of TCS OX2 29 (1, 3.5 and 7 μg/rat) and valproate (26 µg/rat) on stage 3 duration in pentylenetetrazol-kindled rats. TCS OX2 29 at the dose of 7 μg/rat reduced the stage 3 duration. Each bar represents mean ± SEM. **P < 0.01 compared to vehicle-treated rats. In each group n = 7
Fig. 3
Fig. 3
The effect of intracerebroventricular injection of TCS OX2 29 (1, 3.5 and 7 μg/rat) and valproate (26 µg/rat) on stage 3 latency in pentylenetetrazol-kindled rats. TCS OX2 29 at the dose of 7 μg/rat increased latency of 3th stage of seizures. Each bar represents mean ± SEM. **P < 0.01 compared to vehicle-treated rats. In each group n = 7
Fig. 4
Fig. 4
The effect of intracerebroventricular injection of TCS OX2 29 (1, 3.5 and 7 μg/rat) and valproate (26 µg/rat) on stage 4 duration in pentylenetetrazol-kindled rats. TCS OX2 29 at the dose of 7 μg/rat and valproate at the dose of 26 μg/rat decreased duration of 4th stage of seizures. Each bar represents mean ± SEM. *P < 0.05 compared to vehicle-treated rats. In each group n = 7
Fig. 5
Fig. 5
The effect of intracerebroventricular injection of TCS OX2 29 (1, 3.5 and 7 μg/rat) and valproate (26 µg/rat) on stage 4 latency in pentylenetetrazol-kindled rats. TCS OX2 29 at the dose of 7 μg/rat and valproate at the dose of 26 μg/rat increased the latency period of stage 4 seizures. Each bar represents mean ± SEM. **P < 0.01 compared to vehicle-treated rats. In each group n = 7
Fig. 6
Fig. 6
a, b The effect of intracerebroventricular injection of TCS OX2 29 (1, 3.5 and 7 μg/rat) and valproate (26 µg/rat) on anxiety of PTZ-kindled rats. This figure shows PTZ induced anxiety that was not reversed either by TCS OX2 29 (1, 3.5 and 7 μg/rat) or valproate (26 μg/rat). c Shows that the locomotor activity of all groups were similar. Each bar represents mean ± SEM. #P < 0.05 compared to the saline-treated rats. n = 7. PTZ pentylenetetrazol
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