Holtzman and Harlan Sprague-Dawley rats: differences in DRL 72-sec performance and 8-hydroxy-di-propylamino tetralin-induced hypothermia.
Holtzman and Harlan Sprague-Dawley rats: differences in DRL 72-sec performance and 8-hydroxy-di-propylamino tetralin-induced hypothermia.
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发表时间：
1998-08
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通讯作者：
Mercedes BALCELLS-OLIVERO;M. Cousins;L. Seiden
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作者：
Mercedes BALCELLS-OLIVERO;M. Cousins;L. Seiden
几种化合物进行了测试的差异-强化-低速率72秒（DRL 72秒）的时间表，行为筛选，以确定推定的抗抑郁药，这些化合物进行了评估，在两个远交的股票的大鼠，哈兰和霍尔茨曼Sprague-Dawley大鼠。三环类抗抑郁药丙咪嗪和地昔帕明、选择性5-羟色胺（5-HT）再摄取抑制剂氟西汀、5-HT 2受体拮抗剂酮色林、5-HT 1A受体激动剂（+/-）8-羟基-二-丙氨基四氢萘（8-OH-DPAT）和多巴胺释放化合物安非他明的剂量-反应测定在两种大鼠储备中进行了评估。两种大鼠在DRL 72秒时间表上的基线表现不同。哈兰大鼠比Holtzman大鼠具有更高的强化率和更低的反应率。在Holtzman大鼠中，丙咪嗪、酮色林、氟西汀和8-OH-DPAT增加了DRL 72秒时间表的强化率，降低了反应率，但在哈兰大鼠中没有，证实了先前的研究。然而，地昔帕明是在Holtzman和哈兰大鼠中增加强化率和降低反应率的唯一药物;在哈兰大鼠中，主要作用于5-HT系统的药物丙咪嗪、酮色林、氟西汀和8-OH-DPAT破坏了DRL 72秒的性能，并且没有像在Holtzman大鼠中观察到的那样增加超过基线的强化次数。安非他明以类似的方式破坏Holtzman和哈兰大鼠的DRL 72秒表现。还在两种大鼠中评估了对8-OH-DPAT的低温反应; Holtzman大鼠的核心体温下降幅度小于哈兰大鼠。Holtzman和哈兰大鼠之间观察到的行为和药理学差异可能是遗传和/或环境介导的。
Several compounds were tested on the differential-reinforcement-of-low-rate 72-sec (DRL 72-sec) schedule, a behavioral screen to determine putative antidepressants; these compounds were evaluated in two outbred stocks of rats, Harlan and Holtzman Sprague-Dawley rats. A dose-response determination for the tricyclic antidepressants, imipramine and desipramine, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, fluoxetine, the 5-HT2 receptor antagonist, ketanserin, the 5-HT1A receptor agonist, (+/-)8-hydroxy-di-propylamino tetralin (8-OH-DPAT) and the dopamine releasing compound, amphetamine, were assessed in both rat stocks. The two stocks of rats differed in their baseline performance on the DRL 72-sec schedule. The Harlan rats had a higher reinforcement rate and a lower response rate than the Holtzman rats. In Holtzman, but not in Harlan rats, imipramine, ketanserin, fluoxetine and 8-OH-DPAT increased reinforcement rate and decreased response rate on the DRL 72-sec schedule, confirming previous studies. However, desipramine was the only drug to increase reinforcement rate and decrease response rate in both Holtzman and Harlan rats; in Harlan rats, drugs that primarily act upon the 5-HT system, imipramine, ketanserin, fluoxetine and 8-OH-DPAT, disrupted the DRL 72-sec performance and did not increase the number of reinforcements over baseline as was seen in Holtzman rats. Amphetamine disrupted DRL 72-sec performance in both Holtzman and Harlan rats in a similar manner. The hypothermic response to 8-OH-DPAT was also assessed in the two stocks of rats; Holtzman rats had a smaller decrease in core body temperature than Harlan rats. The observed behavioral and pharmacological differences between Holtzman and Harlan rat stocks may be genetically and/or environmentally mediated.