Ataie Zohreh, Babri Shirin, Ghahramanian Golzar Mina, Ebrahimi Hadi, Mirzaie Fariba, Mohaddes Gisou
Neuroscience Research Centre (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
Adv Pharm Bull. 2013;3(2):353-8. doi: 10.5681/apb.2013.057. Epub 2013 Aug 20.
Ghrelin has been shown to have antiepileptic function. However, the underlying mechanisms by which, ghrelin exerts its antiepileptic effects are still unclear. In the present study; we investigated antiepileptic mechanism of ghrelin through GABAB receptors using CGP35348 (selective GABAB receptor antagonist).
Male Wistar rats' hippocampi were bilaterally microinjected with the single dose or 10-day ghrelin (0.3 nmol/µl/side). CGP35348, GABAB receptor antagonist, (12.5 µg/µl/side) or saline injected into the dorsal hippocampus 20 minutes before ghrelin administration. Thirty min after ghrelin microinjection, a single convulsive dose of pentylenetetrazole (PTZ) (50 mg/kg) was injected intraperitoneally (i.p). Afterwards, seizure duration and total seizure score (TSS) were assessed for 30 minutes in all animals.
Our results demonstrated that acute and chronic intrahippocampal (i.h.) injection of ghrelin could significantly (p<0.001) attenuate the severity of seizures. Ghrelin 0.3 nmol/µl/side decreased duration of seizure significantly both in acute (p<0.001) and chronic (p<0.01) injections. The ghrelin antiepileptic effect was completely antagonized by GABAB blockade. The suppression of both duration and TSS induced by ghrelin in hippocampus was significantly (p<0.001) blocked by CGP35348 in PTZ-induced seizures.
In summary, our findings suggest that GABAB receptors may mediate the antiepileptic action of ghrelin in the hippocampus. Therefore, it is possible to speculate that ghrelin acts in the hippocampus to modulate seizures via GABA.
已证实胃饥饿素具有抗癫痫作用。然而，胃饥饿素发挥抗癫痫作用的潜在机制仍不清楚。在本研究中，我们使用CGP35348（选择性GABAB受体拮抗剂）通过GABAB受体研究胃饥饿素的抗癫痫机制。
雄性Wistar大鼠双侧海马微量注射单剂量或10天的胃饥饿素（0.3 nmol/μl/侧）。在给予胃饥饿素前20分钟，将GABAB受体拮抗剂CGP35348（12.5 μg/μl/侧）或生理盐水注入背侧海马。胃饥饿素微量注射30分钟后，腹腔注射（i.p.）单次惊厥剂量的戊四氮（PTZ）（50 mg/kg）。之后，在所有动物中评估30分钟的癫痫持续时间和总癫痫评分（TSS）。
我们的结果表明，急性和慢性海马内（i.h.）注射胃饥饿素可显著（p<0.001）减轻癫痫严重程度。0.3 nmol/μl/侧的胃饥饿素在急性（p<0.001）和慢性（p<0.01）注射中均显著降低癫痫持续时间。GABAB阻断完全拮抗了胃饥饿素的抗癫痫作用。在PTZ诱导的癫痫中，CGP35348显著（p<0.001）阻断了胃饥饿素在海马中诱导的持续时间和TSS的抑制。
总之，我们的研究结果表明，GABAB受体可能介导胃饥饿素在海马中的抗癫痫作用。因此，可以推测胃饥饿素在海马中通过GABA调节癫痫发作。
