Onaivi E S, Maguire P A, Tsai N F, Davies M F, Loew G H
Molecular Research Institute, Palo Alto, CA 94304.
Pharmacol Biochem Behav. 1992 Nov;43(3):825-31. doi: 10.1016/0091-3057(92)90414-b.
The performance of three widely used rat lines (Sprague-Dawley, Wistar, and Long Evans hooded) were evaluated in behavioral test systems that are sensitive to benzodiazepines. The in vivo effects of flunitrazepam and the brain [3H]Ro 15-1788 binding were determined and compared in these rat lines. The behavioral end points evaluated in this study were anxiolysis, measured using the automated elevated plus-maze; sedation by modification of locomotor activity; hyperphagia following food deprivation; protection for pentylenetetrazol-induced convulsions; and hypothermia. There were comparable results in the hypnotic, hypothermic, anticonvulsant, and feeding tests in these lines following flunitrazepam administration. However, the behavior of the Long Evans hooded rat was most amenable to the detection of drug-induced changes in the anxiety test. There was no difference in the maximum number of binding sites (Bmax) or the affinity (Ki) of the Ro 15-1788 or flunitrazepam binding in either the cerebellum or whole brain (minus cerebellum) in the three rat lines as determined by the competitive binding against [3H]Ro 15-1788. Thus, while these rat lines exhibited similar behavioral profiles in most tests the modest differences in the baseline responses and the ability to detect anxiolysis at lower doses of flunitrazepam observed with Long Evans hooded rats makes them particularly suited for these types of studies.
在对苯二氮䓬敏感的行为测试系统中，评估了三种广泛使用的大鼠品系（斯普拉格-道利大鼠、Wistar大鼠和长Evans有帽大鼠）的表现。测定并比较了这三种大鼠品系中氟硝西泮的体内效应以及脑内[3H]Ro 15-1788结合情况。本研究中评估的行为终点包括：使用自动高架十字迷宫测量的抗焦虑作用；通过改变运动活动来测定的镇静作用；禁食后的食欲亢进；对戊四氮诱导惊厥的保护作用；以及体温过低。给予氟硝西泮后，这些品系在催眠、体温过低、抗惊厥和进食测试中得到了可比的结果。然而，长Evans有帽大鼠的行为在焦虑测试中最易于检测到药物诱导的变化。通过与[3H]Ro 15-1788的竞争性结合测定，在这三种大鼠品系的小脑或全脑（减去小脑）中，Ro 15-1788或氟硝西泮结合的最大结合位点数（Bmax）或亲和力（Ki）没有差异。因此，虽然这些大鼠品系在大多数测试中表现出相似的行为特征，但长Evans有帽大鼠在基线反应和在较低剂量氟硝西泮下检测到抗焦虑作用的能力方面存在适度差异，这使得它们特别适合这类研究。
