Verbanac J S, Altman H J, Dhingra P, Harrington G M, Commissaris R L
Department of Pharmaceutical Sciences, College of Pharmacy & AHP, Detroit, MI.
Pharmacol Biochem Behav. 1993 Jun;45(2):429-38. doi: 10.1016/0091-3057(93)90261-q.
The present studies were designed to examine the effects of treatment with the noradrenergic neurotoxin N-(2-chloroethyl)-n-ethyl-2-bromobenzylamine HCl (DSP4; 65 mg/kg, IP) on conflict behavior in the Maudsley reactive (MR) and nonreactive (MNRA) rat strains. In daily 10-min sessions, water-restricted rats were trained to drink water from a tube that was occasionally electrified; electrification was signaled by the presence of a tone (7-s duration; ISI = 30 s). Consistent with previous reports, the number of shocks accepted by rats of the MR and MNRA strains did not differ initially, but MNRA rats exhibited a dramatic increase in punished responding relative to their MR counterparts over the course of several weeks of conflict testing. This MR vs. MNRA strain difference in punished responding did not exhibit extinction following discontinuation of CSD conflict behavior testing for a period of 6 weeks. Whether it was administered after conflict training or before, DSP4 treatment did not reduce the MR vs. MNRA strain difference in conflict behavior; rather, DSP4 treatment tended to increase the magnitude of the MR vs. MNRA difference in conflict behavior. The effects of DSP4 on norepinephrine (NE) and 5-hydroxytrypamine (5-HT) concentrations in the pons medulla region were determined in one group of conflict-experienced MR and MNRA rats (35 weeks after administration) and in a second group of naive MR and MNRA rats (3 weeks after administration). There were no MR vs. MNRA strain differences in NE or 5-HT concentrations in vehicle-treated rats. DSP4 treatment significantly reduced NE, but not 5-HT, concentrations when compared to control values; rats that were sacrificed 3 weeks following DSP4 administration exhibited a greater NE depletion than did rats sacrificed 35 weeks after DSP4 administration. Finally, there were no significant correlations between pons medulla region NE concentrations and conflict behavior in either strain alone or when the data from the two strains were combined. The present results are not consistent with the hypothesis that the MR vs. MNRA strain difference in conflict behavior is the result of strain differences in brain NE function.
本研究旨在检验用去甲肾上腺素能神经毒素N-(2-氯乙基)-N-乙基-2-溴苄胺盐酸盐(DSP4;65毫克/千克,腹腔注射)处理对莫兹利反应性(MR)和非反应性(MNRA)大鼠品系冲突行为的影响。在每天10分钟的实验时段中,对限水大鼠进行训练,使其从偶尔会通电的管子中饮水;通电由一个持续7秒的音调(ISI = 30秒)发出信号。与先前的报告一致,MR和MNRA品系大鼠最初接受的电击次数没有差异,但在数周的冲突测试过程中,MNRA大鼠相对于其MR对应物在受罚反应上表现出显著增加。在停止连续冲突行为测试6周后,这种MR与MNRA品系在受罚反应上的差异并未表现出消退。无论是在冲突训练后还是之前给予DSP4处理,都没有减少MR与MNRA品系在冲突行为上的差异;相反,DSP4处理倾向于增加MR与MNRA在冲突行为上差异的幅度。在一组经历过冲突的MR和MNRA大鼠(给药后35周)以及第二组未经历过冲突的MR和MNRA大鼠(给药后3周)中,测定了DSP4对脑桥延髓区域去甲肾上腺素(NE)和5-羟色胺(5-HT)浓度的影响。在给予载体处理的大鼠中,NE或5-HT浓度没有MR与MNRA品系差异。与对照值相比时,DSP4处理显著降低了NE浓度,但未降低5-HT浓度;DSP4给药后3周处死的大鼠比DSP4给药后35周处死的大鼠表现出更大的NE耗竭。最后,无论是单独在任一品系中,还是将两个品系的数据合并时,脑桥延髓区域NE浓度与冲突行为之间均无显著相关性。目前的结果与以下假设不一致,即MR与MNRA品系在冲突行为上的差异是脑NE功能品系差异的结果。