Vago-vagal Reflexes: Role of CNS GABAB Receptors

描述(申请人提供)：这项研究的首要目标是研究大脑如何控制胃功能。具体地说，这些研究集中在迷走神经反射的中央成分中的GABAB受体。目前的证据表明，GABAB受体是治疗胃病如胃食道反流的潜在靶点(Holloway，2001)。在体内，显微注射技术以及免疫组织化学将被用来确定脑干中的GABAB受体如何影响胃活动。本建议的具体目的是：(1)确定DMV和NTS内微量注射GABAB受体激动剂和拮抗剂对麻醉大鼠胃内压和胃运动的影响；(2)确定GABAB受体激动剂和拮抗剂在DMV和NTS内微量注射时如何对胃运动产生影响的机制；以及(3)确定静脉注射巴氯芬对胃收缩的影响是否部分或完全是由于药物对DMV和/或NTS中GABAB受体的影响。

DESCRIPTION (provided by applicant): The overarching goal of this research is to study how the brain controls gastric function. Specifically, these studies focus on GABAB receptors in the central components of the vago-vagal reflex. Current evidence implicates the GABAB receptor as a potential target for therapeutic interventions for gastric disorders such as gastroesophageal reflux (Holloway, 2001). In vivo microinjection techniques as well as immunohistochemistry will be used to determine how GABAB receptors in the brain stem influence gastric activity. The specific aims of this proposal are to: (1) determine the effects of microinjection of GABAB receptor agonists and antagonists into the DMV and NTS on intragastric pressure and gastric motility of the anesthetized rat; (2) determine the mechanisms underlying how GABAB receptor agonists and antagonists exert their effects on gastric motor activity upon microinjection into the DMV and NTS; and (3) determine whether the effects of intravenous administration of baclofen on gastric contractions are due either in part, or entirely to effects of the drug on GABAB receptors in the DMV and/or NTS.