Study of the effects of alpha2 adrenoceptor on the development of epileptogenesis in immature rats

在人类和动物模型中，抑制性和兴奋性神经递质失衡在癫痫发作的发展中起着重要作用。据报道，中枢去肾上腺素能系统抑制引燃的发展。然而，与成年期相比，产后去甲肾上腺素能系统尚不成熟。因此，为了阐明α -2肾上腺素能受体在未成熟时期癫痫发生发展中的作用，我们研究了不同年龄大鼠（出生后14天、21天、28天和70天）对杏仁核核点燃的影响。α -2激动剂可乐定抑制了28日龄幼鼠和成年大鼠的点火发育。然而，在14日龄幼鼠中，可乐定促进了点火的发展。可乐定与育亨宾、咪唑嗪、劳沃辛等α -2拮抗剂联合给药，可阻断可乐定对14日龄幼鼠引火发育的促进作用。去甲肾上腺素前体羟多巴对14、21日龄大鼠的点火发育无影响。组胺前体1-组氨酸对成年大鼠和14、21日龄幼鼠的点火发育均有抑制作用。目前的药理学研究表明，α -2肾上腺素受体对杏仁核点燃的影响具有年龄特异性。

The imbalance in inhibitory and excitatory neurotransmitters plays an important role in the development of epileptic seizures in human and animal models. Central noradrenergic systems are reported to suppress the development of kindling. However, noradrenergic systems are immature in postnatal period compared with in adult period. Therefore, to elucidate the effect of alpha-2 adrenoceptor on the development of epileptogenesis in immature period, we investigated the effects on the development of amygdaloid kindling in various aged rats (postnatal 14 days, 21 days, 28 days, and 70 days).1. Alpha-2 agonist, clonidine, suppressed the development of kindling in 28-day-old young rats as well as in adult rats. However, the development of kindling was facilitated by clonidine in 14-day-old pup rats.2. Facilitative effect of development of kindling by clonidine in 14-day-old pup rats was blocked with combined administration of clonidine and alpha-2 antagonist such as yohimbine, idazoxan or rauwolscine.3. Noradrenaline precursor droxydopa did not affect the development of kindling in 14-or 21-day-old rats.4. Histamne precursor 1-histidine caused inhibitory effects on the development of kindling in both adult and 14-, 21-day-old pup rats.The present pharmacological studies indicate that the effects of alpha-2 adrenoceptors on the development of amygdaloid kindling are age specific.