Hebert M A, Potegal M, Moore T, Evenson A R, Meyerhoff J L
Division of Neurosciences, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Pharmacol Biochem Behav. 1996 Nov;55(3):405-13. doi: 10.1016/s0091-3057(96)00110-4.
Male hamsters that have been repeatedly defeated by larger, aggressive males subsequently flee from, rather than attack, nonaggressive male intruders that are introduced into their home cages. We have referred to this generalization of flight in response to nonaggressive intruders as "conditioned defeat" (CD). In an attempt to reverse CD pharmacologically, diazepam (DZP) was administered to hamsters at two different time points relative to CD acquisition and subsequent response generalization tests, which involved the exposure of subjects to nonaggressive intruders (NAIs). In Experiment 1, subjects were given a single injection of one of 4 doses of DZP (0, 2, 6, or 20 mg/kg) immediately following CD acquisition. Twenty-four hours later, contrary to expectations, subjects that had received the 6 mg/kg dose displayed elevated flight responses in the presence of an NAI. Flight responding declined over days except in subjects that received the highest dose. In the second experiment, hamsters were administered a single injection of either 0, 2, or 6 mg/kg DZP just prior to a response generalization test occurring 24 h following CD training. Flight responses to the NAIs were again exaggerated in subjects that were given the 6 mg/kg dose, an effect that persisted several days without further drug administration. The present findings suggest the possibility that benzodiazepines can potentiate fear responses under certain stressful conditions.
雄性仓鼠如果多次被体型更大、更具攻击性的雄性仓鼠打败,随后当无攻击性的雄性入侵者被放入它们的笼子时,它们会选择逃离而不是攻击。我们将这种对无攻击性入侵者做出的逃避反应的泛化称为“条件性失败”(CD)。为了从药理学角度逆转条件性失败,我们在与条件性失败习得及随后的反应泛化测试相关的两个不同时间点给仓鼠注射地西泮(DZP),反应泛化测试包括让实验对象接触无攻击性入侵者(NAIs)。在实验1中,在条件性失败习得后,立即给实验对象单次注射4种剂量(0、2、6或20毫克/千克)的DZP中的一种。24小时后,与预期相反,接受6毫克/千克剂量的实验对象在无攻击性入侵者出现时表现出更高的逃避反应。除了接受最高剂量的实验对象外,逃避反应在数天内逐渐下降。在第二个实验中,在条件性失败训练24小时后的反应泛化测试前,给仓鼠单次注射0、2或6毫克/千克的DZP。接受6毫克/千克剂量的实验对象对无攻击性入侵者的逃避反应再次被夸大,这种效应在没有进一步给药的情况下持续了数天。目前的研究结果表明,在某些压力条件下,苯二氮䓬类药物可能会增强恐惧反应。