Commissaris R L, McCloskey T C, Harrington G M, Altman H J
Department of Pharmaceutical Sciences, College of Pharmacy & AHP, Wayne State University, Detroit, MI 48202.
Pharmacol Biochem Behav. 1989 Mar;32(3):801-5. doi: 10.1016/0091-3057(89)90037-3.
The Maudsley Reactive (MR/Har) and Non-Reactive (MNRA/Har) rat strains, selectively bred for differences in open field defecation, have also been shown to differ in their baseline behavior in the Conditioned Suppression of Drinking (CSD) procedure, a second "model" behavior for the study of anxiety and/or emotionality in rats. The present studies were designed to compare the responsiveness of these two strains to the typical antianxiety agent chlordiazepoxide in the CSD paradigm. In daily 10-minute sessions, water-deprived rats were trained to drink from a tube that was occasionally electrified (0.5 mA), electrification being signaled by a tone. Consistent with previous reports, after several weeks of CSD testing, MNRA/Har rats accepted significantly more shocks than did MR/Har rats during control (nondrug) sessions. In both strains, the number of shocks accepted was inversely related to the intensity of the shock used (0.25-1.0 mA), with MNRA/Har rats accepting significantly more shocks than MR/Har rats at all intensities examined. The effects of various doses (1.25-28.4 mg/kg, IP) of chlordiazepoxide were determined in subjects of the MNRA/Har strain at the original training intensity (0.5 mA), while a lower intensity (0.25 mA) was utilized in MR/Har rats. Although punished responding in control (i.e., nondrug) CSD sessions did not differ under these conditions, MNRA/Har rats were found to be more responsive to the anticonflict effects of chlordiazepoxide than rats of the MR/Har strain. This strain difference in anticonflict efficacy of chlordiazepoxide was quite dramatic, with MNRA/Har rats accepting twice as many shocks as MR/Har rats following maximally effective doses of chlordiazepoxide. Low doses of chlordiazepoxide increased water intake slightly, while higher doses decreased water intake. Surprisingly, the chlordiazepoxide-induced depression of water intake was greater in rats of the MR/Har strain. Thus, these Maudsley Reactive and Non-Reactive rat strains, bred originally for their differences in open field behavior, also differ markedly in their responsiveness to chlordiazepoxide in the CSD paradigm. These findings further support the hypothesis that the MR/Har and MNRAHar rat strains may represent a genetically-based "animal model" for the study of emotionality and/or anxiety.
莫兹利反应型(MR/Har)和非反应型(MNRA/Har)大鼠品系,是根据旷场排便差异进行选择性培育的,在条件性饮水抑制(CSD)实验程序中的基线行为也存在差异,CSD是研究大鼠焦虑和/或情绪的第二种“模型”行为。本研究旨在比较这两个品系在CSD范式中对典型抗焦虑药物氯氮卓的反应性。在每天10分钟的实验中,对缺水的大鼠进行训练,使其从偶尔会通电(0.5毫安)的管子中饮水,通电由一个音调发出信号。与之前的报道一致,经过几周的CSD测试后,在对照(无药物)实验中,MNRA/Har大鼠接受的电击比MR/Har大鼠明显更多。在两个品系中,接受的电击次数与所用电击强度(0.25 - 1.0毫安)呈负相关,在所有检测强度下,MNRA/Har大鼠接受的电击都比MR/Har大鼠明显更多。在MNRA/Har品系的大鼠中,以原始训练强度(0.5毫安)测定了各种剂量(1.25 - 28.4毫克/千克,腹腔注射)氯氮卓的效果,而在MR/Har大鼠中使用了较低强度(0.25毫安)。尽管在这些条件下,对照(即无药物)CSD实验中的受罚反应没有差异,但发现MNRA/Har大鼠比MR/Har品系的大鼠对氯氮卓的抗冲突作用更敏感。氯氮卓抗冲突效果的这种品系差异非常显著,在给予最大有效剂量的氯氮卓后,MNRA/Har大鼠接受的电击次数是MR/Har大鼠的两倍。低剂量的氯氮卓会使饮水量略有增加,而高剂量则会使饮水量减少。令人惊讶的是,氯氮卓引起的饮水量减少在MR/Har品系的大鼠中更大。因此,这些最初因旷场行为差异而培育的莫兹利反应型和非反应型大鼠品系,在CSD范式中对氯氮卓的反应性也存在显著差异。这些发现进一步支持了这样的假设,即MR/Har和MNRAHar大鼠品系可能代表了一种基于基因的用于研究情绪和/或焦虑的“动物模型”。