Corticotropin-Releasing Factor in Prepulse Inhibition

超出所提供的空间。精神分裂症患者声惊吓反应的前脉冲抑制在大鼠中，PPI已被用于研究改变脑多巴胺（DA）和5-羟色胺（5-HT）神经传递的药物的效果，因为这些系统与精神分裂症有关。促肾上腺皮质激素释放因子（CRF）改变脑细胞外DA，5-HT和去甲肾上腺素（NE）的浓度，CRF的中枢给药具有许多行为效应。初步数据显示，脑室内（IV）注射CRF可降低Brown Norway（BN）大鼠（基础PPI较低的品系）和Wistar-Kyoto（WKY）大鼠（基础PPI相对较高的品系）的PPI。本实验旨在进一步研究CRF在BN和WKY大鼠PPI中的作用，并探讨CRF引起的PPI降低是否依赖于单胺类神经递质。具体目的一是研究不同剂量的CRF（ICV）对PPI和惊跳幅度的影响，以及外周应用激活垂体/肾上腺轴的CRF是否足以降低PPI。具体目的2是检查CRF拮抗剂（ICV）的给药是否改善BN大鼠的PPI，并检查在CRF给药之前或之后给予拮抗剂是否减弱CRF对PPI的作用。具体目标3是检查选择性消耗单胺（DA、5-HT或NE）或施用作为DA、5-HT或NE受体拮抗剂的药物是否减弱由CRF产生的PPI的降低。具体目标4是评估重复CRF（ICV）是否导致CRF诱导的PPI降低或多巴胺激动剂、氨杂异丁三醇和阿朴吗啡引起的PPI降低的增敏或脱敏。除了检查每种治疗对WKY和BN大鼠PPI的影响外，还将评估每种治疗和大鼠品系对惊吓幅度和CRF诱导的理毛的影响。在单胺耗竭研究中，将通过HPLC评估额叶皮质、海马、丘脑核和下丘脑中的DA、5-HT和NE水平。性能现场=

EXCEED THE SPACE PROVIDED. Prepulse inhibition (PPI) of the acoustic startle response in deficient in patients with schizophrenia. In rats, PPI has been used to study the effetcs of drugs that alter brain dopamine (DA) and serotonin (5-HT) neurotransmission, since these systems are implicated in schizophrenia. Corticotropin-releasing factor (CRF) alters brain extracellular concentrations of DA, 5-HT, and norepinephirne (NE), and central administration of CRF has numerous behavioral effects. Preliminary data show that intracerebroventricular (IV) administration of CRF decreases PPI in both Brown Norway (BN) rats, a strain with low basal PPI, and in Wistar-Kyoto (WKY) rats, a strain with relatively high basasl PPI. Experiments are designed to futher study the role of CRF in PPI in BN and WKY rats, and to examine whether the decrease in PPI caused by CRF is dependent on monoamine neurotransmission. Specific Aim 1 is to eaxmine the effetcs of a range of doses of CRF (ICV) on PPI and startle amplitude, and to examine whether peripheral administration of CRF, which activated the pituitary/adrenal axis, is sufficient to decrese PPI. Specific Aim 2 is to examine whther administraion of a CRF antagonist (ICV) improves PPI in BN rats, and to examine whether administration of the antagonis, either prior to or following CRF administration, attenuates the effect of CRF on PPI. Specific Aim 3 is to examine whether selective depletion of the monoamines (DA, 5-HT, or NE), or adminstration of drugs that are antagonists at DA, 5-HT or NE receptors attenuates the decrease in PPI produced by CRF. Specific Aim 4 is to assess whether repeated CRF (ICV) results in sensitization or desensitization of the CRF-induced decrease in PPI or of the decrese in PPI caasued by adminstration of the dopamine agonists, amhetamine and apomorphine. In addition to examining the effects of each treatment on PPI in both WKY and BN rats, effects of eac tratment and of rat strain on startle amplitude and CRF-induced grooming willl be assessed. In the monoamine depletion studies, levels of DA, 5-HT, and NE in frontal cortex, hippocampus, nucleus accumbens and hypothalamus will be assessed by HPLC. PERFORMANCE SITE ========================================Section End===========================================