Bialik R J, Pappas B A, Pusztay W
Pharmacol Biochem Behav. 1982 Feb;16(2):279-83. doi: 10.1016/0091-3057(82)90161-7.
The effects of chlordiazepoxide (CDZ) in extinction and punishment-conflict tasks were examined in rats after neonatal systemic administration of 6-hydroxydopamine (6-OHDA) to deplete forebrain norepinephrine (NE). At about 70 days of age the rats were water deprived and trained for three days to drink in a novel apparatus. On the fourth day (test day) drinking was either extinguished by elimination of water from the drinking tube or punished by lick-contingent shock. Just prior to this test session half of the vehicle and half of the 6-OHDA treated rats were given an injection of CDZ (8 mg/kg IP). Both the injection of CDZ and forebrain NE depletion prolonged responding during extinction and reduced the suppressant effects of punishment in male rats, and these effects were of similar magnitude. Furthermore, CDZ was as effective in neonatal 6-OHDA treated male rats as in vehicle treated rats indicating that decreased transmission is ascending NE fibers caused by CDZ is not solely responsible for its behavioral effects in extinction and conflict tasks. Rather, these effects may involve cooperative mediation by both noradrenergic and serotonergic forebrain terminals. Unexpectedly, CDZ's anti-extinction effect was absent in female rats and its anti-conflict effect observed only in NE depleted females.
在新生大鼠全身注射6-羟基多巴胺(6-OHDA)以耗尽前脑去甲肾上腺素(NE)后,研究了氯氮卓(CDZ)在消退和惩罚冲突任务中的作用。在大约70日龄时,大鼠被剥夺水分,并在一个新装置中训练三天以进行饮水。在第四天(测试日),通过从饮水管中去除水来使饮水消退,或者通过舔舐引发的电击来惩罚饮水。就在这个测试环节之前,一半的溶剂对照组和一半的6-OHDA处理组大鼠被注射了CDZ(8毫克/千克,腹腔注射)。注射CDZ和前脑NE耗竭都延长了雄性大鼠在消退过程中的反应,并降低了惩罚的抑制作用,而且这些作用的程度相似。此外,CDZ在新生6-OHDA处理的雄性大鼠中与在溶剂对照组大鼠中一样有效,这表明CDZ导致的上行NE纤维传递减少并非其在消退和冲突任务中行为效应的唯一原因。相反,这些效应可能涉及去甲肾上腺素能和血清素能前脑终末的协同介导。出乎意料的是,CDZ的抗消退效应在雌性大鼠中不存在,其抗冲突效应仅在NE耗竭的雌性大鼠中观察到。