Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Pharmacol Rep. 2017 Aug;69(4):757-763. doi: 10.1016/j.pharep.2017.03.003. Epub 2017 Mar 12.
In addition to its role as a circulating hormone, oxytocin can also act as a neurotransmitter and a neuromodulator within the brain. In this study, we investigated the intra-hippocampal effect of oxytocin on an experimental seizure model induced by pentylenetetrazole (PTZ) in rats. We also used atosiban (oxytocin antagonist), diazepam and flumazenil (gamma-aminobutyric acid or GABA-benzodiazepine receptor agonist and antagonist, respectively) to clarify the involved mechanism.
In ketamine-xylazine anesthetized rats, the right and left sides of the dorsal hippocampus (CA1) were implanted with two guide cannulas. Epileptic behaviors were induced by intraperitoneal (ip) injection of PTZ (60mg/kg), and the latency time to onset of first myoclonic jerk, and the duration of epileptic seizures were determined for 30min.
Intra-hippocampal microinjections of oxytocin at doses of 10 and 20ng/site, diazepam (100 and 200ng/site) and co-administration of their ineffective doses significantly (p<0.01) increased the onset of first myoclonic jerk and decreased duration of epileptic seizure. Antiepileptic effects of oxytocin (20ng/site) were inhibited by atosiban (20 and 40ng/site) and flumazenil (100 and 200ng/site) pretreatments. On the other hand, prior administration of flumazenil (100 and 200ng/site) and atosiban (20 and 40ng/site) prevented the antiepileptic effects induced by diazepam (100 and 200ng/site).
The results of the present study showed that at the level of the hippocampus oxytocin suppressed the severity of epileptic behaviors. A hippocampal GABA-benzodiazepine receptor mechanism may be involved in antiepileptic effect of oxytocin.
除了作为一种循环激素外，催产素也可以在大脑内作为神经递质和神经调质发挥作用。在这项研究中，我们研究了催产素对戊四氮（PTZ）诱导的大鼠实验性癫痫模型的海马内作用。我们还使用阿托西班（催产素拮抗剂）、地西泮和氟马西尼（γ-氨基丁酸或 GABA-苯二氮䓬受体激动剂和拮抗剂）来阐明所涉及的机制。
在氯胺酮-甲苯噻嗪麻醉的大鼠中，在背侧海马（CA1）的右侧和左侧植入两个导向套管。通过腹腔（ip）注射 PTZ（60mg/kg）诱导癫痫发作，确定首次肌阵挛抽搐发作的潜伏期和癫痫发作的持续时间为 30min。
海马内微注射催产素 10 和 20ng/部位、地西泮（100 和 200ng/部位）和无效剂量的联合应用显著（p<0.01）增加了首次肌阵挛抽搐的发作和减少了癫痫发作的持续时间。催产素（20ng/部位）的抗癫痫作用被阿托西班（20 和 40ng/部位）和氟马西尼（100 和 200ng/部位）预处理所抑制。另一方面，氟马西尼（100 和 200ng/部位）和阿托西班（20 和 40ng/部位）的预先给药防止了地西泮（100 和 200ng/部位）诱导的抗癫痫作用。
本研究结果表明，在海马水平上，催产素抑制了癫痫行为的严重程度。海马 GABA-苯二氮䓬受体机制可能参与了催产素的抗癫痫作用。
