BNST GluN2B and CRF signaling in the antidepressant actions of ketamine

描述（由申请人提供）：抑郁症是一种主要的健康问题。传统的药理学治疗以选择性再摄取抑制剂作为儿茶酚胺系统的靶点，但这些方法的缺点是：a)需要延长治疗才能达到疗效，b)通常需要持续给药，以及c)相当大比例的临床人群具有治疗耐药性。在过去的几年里，随着氯胺酮作为抗抑郁药的出现，谷氨酸神经递质系统得到了越来越多的关注。氯胺酮是谷氨酸受体NMDA类的拮抗剂，它的优势在于它既快速起作用，又在单次剂量后产生持久的作用。

DESCRIPTION (provided by applicant): Depression is a major health problem. Traditional pharmacological treatments have targeted the catecholamine systems with selective reuptake inhibitors, but these have the disadvantages that a) they take extended treatment to achieve efficacy, b) they often require continued dosing, and c) a significant proportion of the clinical population is treatment resistant. The glutamate neurotransmitter system has gained increased attention in the last several years with the advent of the use of the drug ketamine as an antidepressant. Ketamine, which is an antagonist of the NMDA class of glutamate receptors, is advantageous in that it is both rapidly acting and produces persistent effects after a single dose. Animal model studies suggest that ketamine works by producing homeostatic plasticity at glutamate synapses, however the key circuits modified to produce antidepressant actions are not clear. In this proposal we test the hypothesis that NMDA receptors in a region of the brain known as the bed nucleus of the stria terminalis play a key role in the antidepressant actions of ketamine. Moreover, we propose that this occurs via an interaction with the corticotropin receptor factor (CRF) system in this region.