Conti Lisa H, Murry Jennifer D, Ruiz Mark A, Printz Morton P
Department of Pharmacology, 0636, University of California, San Diego, 9500 Gilman Drive, La Jolla 92093, USA.
Psychopharmacology (Berl). 2002 May;161(3):296-303. doi: 10.1007/s00213-002-1025-2. Epub 2002 Mar 28.
Prepulse inhibition (PPI) of the acoustic startle response is altered by manipulations that affect brain monoamine neurotransmission. Corticotropin-releasing factor (CRF), a neurotransmitter that is released during stress, and CRF receptors are expressed in areas of the brain which contribute to PPI, and central administration of CRF changes extracellular concentrations of the monoamines. Therefore, CRF is in a position to alter PPI, either by causing the release of other neurotransmitters, or by direct effects at CRF receptors.
The present experiments were conducted to test the hypothesis that intracerebroventricular (ICV) administration of CRF would decrease PPI in rats. Additionally, these experiments were used to examine whether CRF results in differential changes in PPI in rat strains that show high and low basal PPI, and whether CRF-induced grooming behavior and increased startle amplitude are also strain-dependent.
Male Wistar-Kyoto (WKY) rats inbred in our colony in La Jolla, WKY rats obtained from Charles River, and Brown Norway (BN) rats from Harlan, Sprague-Dawley were tested for grooming behavior, PPI and startle amplitude following ICV infusion of either CRF (1.0-3.0 microg) or saline.
CRF significantly decreased PPI in both BN rats, which show relatively little PPI in the basal condition and, in WKY rats. The amplitude of the acoustic startle response was increased in WKY rats only and, only by the 3.0 microg dose of CRF. CRF increased grooming behavior in the La Jolla colony WKY and BN rats. However, within the time frame during which the rats were being observed, CRF failed to significantly increase grooming in Charles River WKY rats.
CRF diminished PPI of the acoustic startle response in rats that show high (WKY) and low (BN) basal PPI. This effect does not appear to be dependant on CRF-induced changes in startle amplitude. The results suggest the possibility that stress-induced exacerbation of symptoms in schizophrenia, which is characterized by deficient PPI, may be CRF-dependent.
影响脑单胺神经传递的操作会改变听觉惊吓反应的前脉冲抑制（PPI）。促肾上腺皮质激素释放因子（CRF）是一种在应激时释放的神经递质，CRF及其受体在对PPI有影响的脑区表达，并且向脑内注射CRF会改变单胺的细胞外浓度。因此，CRF有可能通过引起其他神经递质的释放或通过对CRF受体的直接作用来改变PPI。
进行本实验以检验以下假设：向大鼠脑室内（ICV）注射CRF会降低大鼠的PPI。此外，这些实验还用于研究CRF是否会在基础PPI高和低的大鼠品系中导致PPI的差异变化，以及CRF诱导的梳理行为和惊吓幅度增加是否也依赖于品系。
对在拉霍亚我们的实验种群中繁殖的雄性Wistar-Kyoto（WKY）大鼠、从查尔斯河获得的WKY大鼠以及来自哈兰的Brown Norway（BN）大鼠、Sprague-Dawley大鼠，在ICV注射CRF（1.0 - 3.0微克）或生理盐水后，测试其梳理行为、PPI和惊吓幅度。
CRF显著降低了BN大鼠（其在基础状态下PPI相对较低）和WKY大鼠的PPI。仅在WKY大鼠中，听觉惊吓反应的幅度增加，且仅在CRF剂量为3.0微克时增加。CRF增加了拉霍亚种群的WKY和BN大鼠的梳理行为。然而，在观察大鼠的时间范围内，CRF未能显著增加查尔斯河WKY大鼠的梳理行为。
CRF降低了基础PPI高（WKY）和低（BN）的大鼠的听觉惊吓反应的PPI。这种效应似乎不依赖于CRF诱导的惊吓幅度变化。结果表明，以PPI缺陷为特征的精神分裂症中应激诱导的症状加重可能与CRF有关。
