MAUDSLEY RATS, BENZODIAZEPINES AND CONFLICT BEHAVIOR

莫德斯利老鼠品系可能是世界上最保守的秘密之一 生物精神病学。布罗德赫斯特在20世纪50年代选择性地培育了 和20世纪60年代的高水平和低水平的情绪化(开放 野外排便：莫德斯利反应性和非反应性 大鼠代表了一种基于遗传的“动物模型”，用于研究糖尿病 焦虑症。令人惊讶的是，关于行为的报道 这些毛斯利大鼠的药理作用并不存在。这也许是 因为与OFD测试相关的两个问题：(1)它确实 不适合重复措施设计和(2)“地板效应” (即无反应大鼠的零排便)，这使得药物 难以解释的操纵行为。使用三个选项中的两个 戈登·哈林顿博士在 北爱荷华大学一直在繁衍后代，我们已经证明 非反应性(MNRA/HAR)大鼠不同于反应性(MR/HAR)大鼠 大鼠在其基础表现中的条件性抑制 饮酒(CSD)范式，MNRA/HAR大鼠接受 电击次数比MR/HAR大鼠多。此CSD程序与以下相关 已经使用了Vogel和Geller-Seifter程序 广泛研究“焦虑”和抗焦虑药剂。这个 本研究的第一个目标是确定基本的 哈林顿氏第二非反应性应变的CSD表现 (mnr/har)。这些结果将阐明两国之间的关系 OFD和CSD行为之间的关系。最后，因为惩教署 过程是非零基线过程，使用重复的 措施，一系列行为药理学研究将 指挥。具体地说，苯二氮卓类激动剂的作用， 苯二氮卓类拮抗剂Ro15-1788 “反向激动剂”(FG-7142和CGS-8216)，巴比妥酸盐 在这三个Maudsley大鼠品系中被确定。基于 无反应性患者苯二氮卓类受体数目增多 与反应性大鼠相比，非反应性大鼠应 对苯二氮卓类激动剂和 反向激动剂。单剂量安定的初步数据 (5毫克/公斤)表明情况可能是这样。巴比妥酸盐 代表“对照”，预计不会出现应变差异。 这些研究的结果将大大提高我们的 对它们的行为和药理的了解 Maudsley老鼠品系，并将开辟额外的基本领域 对焦虑症的性质和临床研究 情绪化行为。

The Maudsley rat strains may be one of the best-kept secrets in Biological Psychiatry. Selectively bred by Broadhurst in the 1950s and 1960s for their high and low levels of emotionality (Open Field Defecation; OFD), the Maudsley Reactive and Non-Reactive rats represent a genetically-based "animal model" for the study of anxiety disorders. Surprisingly, reports on the behavioral pharmacology of these Maudsley rats do not exist. This is perhaps because of two problems associated with OFD testing: (1) it does not lend itself to repeated measures designs and (2) "floor effects" (i.e., zero defecation in the Non-Reactive rats), which make drug manipulations difficult to interpret. Using two of the three strains of Maudsley rats which Dr. Gordon Harrington at the University of North Iowa has been breeding, we have shown that Non-Reactive (MNRA/Har) rats differ from Reactive (MR/Har) rats in their basal performance in the Conditional Suppression of Drinking (CSD) paradigm, with the MNRA/Har rats accepting more shocks than MR/Har rats. This CSD procedure, related to the Vogel and Geller-Seifter procedures, has been used extensively in the study of "anxiety" and anti-anxiety agents. The first objective of the present studies is to determine the basal CSD performance of Harrington's second Non-Reactive strain (MNR/Har). These results will shed light on the relationship between OFD and CSD behavior. Finally, because the CSD procedure is a non-zero baseline procedure employing repeated measures, a series of behavioral pharmacology studies will be conducted. Specifically, the effects of benzodiazepine agonists, the benzodiazepine antagonist Ro15-1788, benzodiazepine "inverse agonists" (FG-7142 and CGS-8216), and barbiturates will be determined in these three Maudsley rat strains. Based on the greater number of benzodiazepine receptors in the Non-Reactive rats compared to the Reactive rats, the Non-Reactive rats should show a greater response to both the benzodiazepine agonists and inverse agonists. Preliminary data with a single dose of diazepam (5 mg/kg) suggest that this may be the case. The barbiturates represent "controls", with no strain differences expected to occur. The results of these studies will greatly enhance our understanding of the behavior and pharmacology of these Maudsley rat strains, and will open up areas for additional basic and clinical investigations into the nature of anxiety disorders and emotional behavior.