Commissaris Randall L, Fomum Elizabeth A, Leavell Bonita J
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan 48202, USA.
Depress Anxiety. 2004;19(3):146-51. doi: 10.1002/da.20006.
The startle potentiated startle (SPS) paradigm has been reported to be an effective procedure for studying the conditioned enhancement of acoustic startle in the absence of electric shocks or extinction. This study examines the effects of two anxiolytic treatments, buspirone and alprazolam, on this SPS effect. Subjects were tested in the SPS paradigm 2 days a week (Monday and Thursday) for 10 weeks. Each startle test session consisted of 10 Noise Alone trials (115 dB acoustic noise burst presented for 40 ms) and 10 Light+Noise trials (115 dB acoustic stimuli presented during the latter 40 ms of a 3,540 ms period in which a 15-watt light was illuminated). Although there was no difference in startle amplitude on Noise Alone trials when compared to Light+Noise trials initially, by the end of the first test session and continuing throughout the duration of the experiment, startle amplitude on Light+Noise trials was significantly (approximately 50-75%) greater than on Noise Alone trials. After five control (i.e., no injection) SPS test sessions, once-weekly drug challenges were conducted over the course of 7 weeks. In these weekly drug challenges, subjects received acute treatment with various doses of the benzodiazepine anxiolytic alprazolam (0.25, 0.5, 1.0 mg/kg) or the novel anxiolytic buspirone (1.0, 2.0, 4.0 mg/kg); subjects also received vehicle treatment (0.5% methylcellulose) on one treatment day. All treatments were administered intraperitoneally (i.p.), 15 min before the start of startle testing. Consistent with previous reports, buspirone increased and alprazolam decreased startle amplitude on the Noise Alone trials; these effects were dose-related. Both agents reduced the magnitude of the SPS effect when it was expressed as the Light+Noise startle amplitude minus the Noise Alone startle amplitude. These findings are similar to the effects of these treatments in the traditional shock-based fear-potentiated startle paradigm.
据报道,惊吓增强惊吓(SPS)范式是一种在无电击或消退情况下研究听觉惊吓条件增强的有效程序。本研究考察了两种抗焦虑药物——丁螺环酮和阿普唑仑——对这种SPS效应的影响。受试者每周2天(周一和周四)在SPS范式下接受测试,为期10周。每次惊吓测试环节包括10次仅噪声试验(呈现40毫秒的115分贝突发声学噪声)和10次光+噪声试验(在15瓦灯光亮起的3540毫秒时间段的后40毫秒呈现115分贝声学刺激)。尽管最初仅噪声试验中的惊吓幅度与光+噪声试验相比没有差异,但在第一个测试环节结束时并在整个实验过程中,光+噪声试验中的惊吓幅度显著(约50 - 75%)大于仅噪声试验中的惊吓幅度。在进行五次对照(即不注射)SPS测试环节后,在7周的过程中每周进行一次药物激发试验。在这些每周一次的药物激发试验中,受试者接受不同剂量的苯二氮䓬类抗焦虑药物阿普唑仑(0.25、0.5、1.0毫克/千克)或新型抗焦虑药物丁螺环酮(1.0、2.0、4.0毫克/千克)的急性治疗;受试者在一个治疗日还接受了赋形剂治疗(0.5%甲基纤维素)。所有治疗均在惊吓测试开始前15分钟腹腔注射(i.p.)。与先前的报道一致,丁螺环酮增加而阿普唑仑降低了仅噪声试验中的惊吓幅度;这些效应与剂量相关。当将SPS效应表示为光+噪声惊吓幅度减去仅噪声惊吓幅度时,两种药物均降低了SPS效应的幅度。这些发现与这些治疗在传统的基于电击的恐惧增强惊吓范式中的效应相似。