POSTNATAL DEVELOPMENT OF THE GABA RECEPTOR COMPLEX

越来越多的证据表明，胎儿接触抗癫痫药物 可能会在行为上产生长期甚至永久性的改变， 发育中动物中枢神经系统的神经元活动和/或生物化学。 由于抗惊厥药物至少通过以下途径发挥部分作用 改变GABA在突触后受体的有效性，目的是 所提议的研究的目的是确定特定刺激或 在个体发育过程中阻断GABA受体可能会影响出生后 GABA系统的开发。这项研究将集中在 突触后GABA受体复合体(GABA-PRC)在脑内的发育 它有一个明确的GABA能输入，即中缝背核(DRN)。这个 将使用放射性配基研究DRN中GABA受体的存在 识别和量化其外观的绑定方法。的亚单位 GABA-PRC将从不同出生年龄的动物身上表现出来 在从DRN区制备的膜和DRN区的切片中 通过体外放射自显影。职能责任感的出现 的GABA能受体将用单一的电生理方法进行评估 DRN内的细胞记录和微离子电泳法 5-羟色胺能神经元对GABA和GABA的敏感性 GABA类似物将在完整的动物和体外切片上进行测试 准备工作。这些数据将提供有关 大脑皮层突触后GABA受体的出现和功能发育 DRN.产前暴露于GABA激动剂和拮抗剂对大鼠脑血管紧张素转换酶活性的影响 然后将检查这个核团中神经元的出生后发育情况。 用药仔鼠DRN中GABA-PRC的出现和成熟 会与年龄相匹配的相应网站进行表征和比较 控制动物。产前暴露和配对的对照幼崽将被 比较出生后发育过程中的电生理学功能 DRN神经元中GABA反应性的成熟。通过检查影响 专门改变GABA的药物的产前给药 突触传递在突触后受体发育中的作用 敏感度：有可能确定与 GABA系统的发育变化。

Accumulating evidence suggests that fetal exposure to antiepileptic drugs may produce long-lasting or even permanent alterations in behavior, neuronal activity and/or biochemistry of the CNS of the developing animal. Since anticonvulsant medications exert at least some of their effects by altering the effectiveness of GABA at postsynaptic receptors, the purpose of the proposed studies is to determine whether specific stimulation or blockade of GABA receptors during ontogeny could affect the postnatal development of the GABA system. This research will focus on the development of the postsynaptic GABA receptor complex (GABA-PRC) in an area which has a defined GABAergic input, the dorsal raphe nucleus (DRN). The presence of GABA receptors will be studied in the DRN using radioligand binding methods to identify and quantify their appearance. Subunits of the GABA-PRC will be characterized from animals at different postnatal ages both in membranes prepared from the DRN area and in slices of the DRN area by in vitro autoradiography. The appearance of functional responsivitity of GABAergic receptors will be assessed electrophysiologically using single cell recording and microiontophoretic techniques within the DRN of developing rats; the sensitivity of 5-HT containing neurons to GABA and GABA analogs will be tested in intact animals and in vitro slice preparations. These data will provide unique information about the appearance and functional development of postsynaptic GABA receptors in the DRN. The effect of prenatal exposure to GABA agonists and antagonists on postnatal development of neurons in this nucleus will then be examined. The appearance and maturation of the GABA-PRC in the DRN from treated pups will be characterized and compared with corresponding sites in age-matched control animals. Prenatally exposed and paired control pups will be compared electrophysiologically during postnatal development for functional maturation of GABA responsivity in DRN neurons. By examining the effects of the prenatal administration of drugs which specifically alter GABA synaptic transmission on the development of postsynaptic receptor sensitivity it may be possible to identify pathologies associated with developmental alterations in the GABA system.