Mattingly B A, Fields S E, Langfels M S, Rowlett J K, Robinet P M, Bardo M T
Department of Psychology, Morehead State University, KY 40351-1689, USA.
Psychopharmacology (Berl). 1996 May;125(1):33-42. doi: 10.1007/BF02247390.
Male Wistar rats (250-350 g) were injected (SC) daily with the putative selective dopamine D3 receptor agonist, 7-OH-DPAT (0.01, 0.10, or 1.0 g/kg) or vehicle for 10 days. Fifteen minutes after each injection, the rats were tested for locomotor activity in photocell arenas for 20 min or 2 h. In two experiments, following this subchronic treatment, all rats received a challenge injection of apomorphine (1.0 mg/kg, SC), or cocaine (10 mg/kg, IP) on day 11, and were tested for locomotor activity. In a third experiment, dopamine synthesis in striatal and mesolimbic (nucleus accumbens-olfactory turbercle) tissue was assessed following acute or chronic 7-OH-DPAT treatments by measuring the accumulation of dihydroxyphenylalanine (DOPA) after treatment with a DOPA decarboxylase inhibitor. Major findings were as follows: a) acute 7-OH-DPAT treatment produced a dose-dependent decrease in locomotor activity; b) when tested for 2 h, the 1.0 mg/kg dose of 7-OH-DPAT produced a progressively greater increase in activity across the 10 test days (i.e., behavioral sensitization); c) subchronic treatment with 7-OH-DPAT did not result in cross-sensitization to either apomorphine or cocaine; d) acute treatment with the 1.0 mg/kg dose of 7-OH-DPAT significantly decreased dopamine synthesis in both striatal and mesolimbic regions; and e) chronic 7-OH-DPAT treatments did not affect basal dopamine synthesis in either brain region. Although the behavioral effects of 7-OH-DPAT were similar to the reported effects of the D2/D3 dopamine agonist quinpirole, the effects of repeated 7-OH-DPAT treatments differed from those of quinpirole in terms of cross-sensitization and basal dopamine synthesis. These results suggest that locomotor inhibition produced by low doses of 7-OH-DPAT is not related to dopamine autoreceptor stimulation, and the development of behavioral sensitization to high doses of 7-OH-DPAT is not due to the development of dopamine autoreceptor subsensitivity.
雄性Wistar大鼠（250 - 350克）每天皮下注射假定的选择性多巴胺D3受体激动剂7 - OH - DPAT（0.01、0.10或1.0克/千克）或赋形剂，持续10天。每次注射后15分钟，将大鼠置于光电活动场内测试20分钟或2小时的运动活性。在两个实验中，经过这种亚慢性治疗后，所有大鼠在第11天接受阿扑吗啡（1.0毫克/千克，皮下注射）或可卡因（10毫克/千克，腹腔注射）的激发注射，并测试其运动活性。在第三个实验中，通过测量用多巴脱羧酶抑制剂处理后二羟基苯丙氨酸（DOPA）的积累，评估急性或慢性7 - OH - DPAT处理后纹状体和中脑边缘（伏隔核 - 嗅结节）组织中的多巴胺合成。主要发现如下：a）急性7 - OH - DPAT处理导致运动活性呈剂量依赖性降低；b）当测试2小时时，1.0毫克/千克剂量的7 - OH - DPAT在10个测试日内使活性逐渐增加（即行为敏化）；c）7 - OH - DPAT亚慢性处理未导致对阿扑吗啡或可卡因的交叉敏化；d）1.0毫克/千克剂量的7 - OH - DPAT急性处理显著降低纹状体和中脑边缘区域的多巴胺合成；e）慢性7 - OH - DPAT处理未影响任一脑区的基础多巴胺合成。尽管7 - OH - DPAT的行为效应与已报道的D2/D3多巴胺激动剂喹吡罗的效应相似，但重复7 - OH - DPAT处理在交叉敏化和基础多巴胺合成方面的效应与喹吡罗不同。这些结果表明，低剂量7 - OH - DPAT产生的运动抑制与多巴胺自身受体刺激无关，对高剂量7 - OH - DPAT行为敏化的发展并非由于多巴胺自身受体敏感性降低。
