Goudarzi Elham, Elahdadi Salmani Mahmoud, Lashkarbolouki Taghi, Goudarzi Iran
Faculty of Biology, Damghan University, Damghan, Iran.
Faculty of Biology, Damghan University, Damghan, Iran.
Pharmacol Biochem Behav. 2015 Mar;130:77-83. doi: 10.1016/j.pbb.2015.01.006. Epub 2015 Jan 17.
Orexin has been shown to be involved in a number of physiological and behavioral processes including, feeding and metabolism, reward, nociception, and anxiety. Furthermore, orexin can cause increased neuronal excitability that gives rise to epileptic activity. The distribution of orexin receptor expression in the hippocampus, suggests a possible importance of orexin in the control of seizures in the temporal lobe epilepsy. Therefore, in this study, the effect of hippocampal orexin 1 and 2 receptors on seizure and glutamate and GABA (gamma-aminobutyric acid) contents was explored.
Orexin 1 receptor (OX1R) antagonist (SB) and OX2R antagonist (TCS) were administrated bilaterally through separate cannulae into both hippocampi. Behavioral convulsions were provoked by intravenous pentylenetetrazol (PTZ) application model. The amount of total hippocampal glutamate and GABA contents was then measured by a biochemical method.
SB (50 nmol) infusion reduced seizure stage, duration and decreased glutamate while GABA content was increased. SB (200 nmol) also reduced seizure stage, duration and glutamate content, without change of GABA content. TCS (20 nmol) infusion reduced seizure stage and duration without concomitant change in glutamate and GABA contents. Further, TCS (40 nmol) did neither affect the seizure nor the GABA, while decreased glutamate content. Co-administration of SB (50 nmol) with TCS (40 nmol) and also SB (200 nmol) with TCS (40 nmol) reduced seizure stage, duration and glutamate, but increased GABA content.
It is concluded that OX1R and OX2R antagonists reduce convulsive intensity, partially through alterations of hippocampal glutamate and GABA contents.
食欲素已被证明参与多种生理和行为过程，包括进食与代谢、奖赏、痛觉感受和焦虑。此外，食欲素可导致神经元兴奋性增加，进而引发癫痫活动。食欲素受体在海马体中的表达分布表明，食欲素在颞叶癫痫发作控制中可能具有重要作用。因此，在本研究中，探讨了海马体中食欲素1型和2型受体对癫痫发作以及谷氨酸和γ-氨基丁酸（GABA）含量的影响。
通过单独的套管将食欲素1型受体（OX1R）拮抗剂（SB）和OX2R拮抗剂（TCS）双侧注入海马体。采用静脉注射戊四氮（PTZ）模型诱发行为性惊厥。然后通过生化方法测量海马体中谷氨酸和GABA的总含量。
注入SB（50 nmol）可降低癫痫发作阶段、持续时间，并降低谷氨酸含量，同时GABA含量增加。注入SB（200 nmol）也可降低癫痫发作阶段、持续时间和谷氨酸含量，而GABA含量无变化。注入TCS（20 nmol）可降低癫痫发作阶段和持续时间，而谷氨酸和GABA含量无相应变化。此外，TCS（40 nmol）既不影响癫痫发作，也不影响GABA含量，但可降低谷氨酸含量。将SB（50 nmol）与TCS（40 nmol）联合使用，以及将SB（200 nmol）与TCS（40 nmol）联合使用，均可降低癫痫发作阶段、持续时间和谷氨酸含量，但可增加GABA含量。
得出结论，OX1R和OX2R拮抗剂可降低惊厥强度，部分是通过改变海马体中谷氨酸和GABA的含量实现的。
