SOCIAL REACTIVITY AND D(1) DOPAMINE-RECEPTORS - STUDIES IN MICE SELECTIVELY BRED FOR HIGH AND LOW-LEVELS OF AGGRESSION
SOCIAL REACTIVITY AND D(1) DOPAMINE-RECEPTORS - STUDIES IN MICE SELECTIVELY BRED FOR HIGH AND LOW-LEVELS OF AGGRESSION
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DOI：
10.1038/npp.1994.13
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发表时间：
1994-04-01
影响因子：
7.6
通讯作者：
MAILMAN, RB
中科院分区：
文献类型：
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作者：
LEWIS, MH;GARIEPY, JL;MAILMAN, RB
通过选择性培育癌症研究所小鼠的高攻击性和低攻击性，获得了社会行为的显着个体差异。如前所述，当与未经选择的群养伙伴小鼠配对时，NC900 小鼠表现出孤立诱导的攻击性。相反，NC100 小鼠无法攻击，在社交接触时会僵住。先前的研究已证实 NC100 小鼠伏核和尾状核中的多巴胺浓度较低，而这些相同区域的多巴胺受体密度增加。因此，我们希望确定施用多巴胺受体激动剂对社会行为的影响。这两个品系的小鼠均被给予 0、1、3 或 10 mg/kg (SC) 的全效 D-1 受体激动剂二羟西定，并在社交互动测试中评估它们的行为。 DiHydrexidine 以剂量依赖性方式减少 NC900 小鼠的攻击性和 NC100 小鼠的非对抗性方法。在洗澡的情况下，这是由于对轻微的社交刺激产生了明显的反应，通过逃跑、反射性踢腿和发声等行为的增加来衡量。二羟西定对低攻击性细粒的冻结行为特征没有系统影响。在独立实验中，小鼠用 D-1 拮抗剂 SCH-23390 (0.1 mg/kg) 或选择性 D-2 拮抗剂瑞莫必利 (1.0 mg/kg) 进行预处理，然后接受二羟西定 (10 mg/kg) 并按上述方法进行测试。 SCH-23390 显着拮抗二羟西定对两个品系小鼠社会反应性的影响，但不被瑞莫必利减弱。拮抗剂预处理既不能恢复 NC900 系中的攻击，也不能恢复 NC100 系中的非拮抗接近行为，这表明 D-1/D-2 相互作用对于启动行动的重要性。这些研究表明 D-1 多巴胺受体在对社会刺激的情绪反应中发挥着重要作用。
Robust individual differences in social behavior have been obtained by selectively breeding Institute for cancer Research mice for high and low levels of aggression. As previously shown, when paired with a non-selected, group-housed partner mouse, NC900 mice exhibit isolation-induced aggression. Conversely, NC100 mice fail to attack, freezing upon social contact. Previous studies have established that NC100 mice have lower dopamine concentrations in nucleus accumbens and caudate nucleus, with increased dopamine receptor densities in these same regions. Thus, we wished to determine the effect of administration of a dopamine receptor agonist on social behavior. Mice of both lines were administered 0, 1, 3, or 10 mg/kg (SC) of the full efficacy D-1 receptor agonist dihydrexidine, and their behavior was assessed in a social interaction test. Dihydrexidine reduced aggression in NC900 mice and nonagonistic approach in NC100 mice in a dose dependent manner. In bath cases, this resulted from induction of a marked reactivity to mild social stimulation as measured by increases in behaviors such as escape, reflexive kicking, and vocalizations. Dihydrexidine had no systematic effect on the freezing behavior characteristic of the low-aggressive fine. In independent experiments, mice were pretreated with either the D-1 antagonist SCH-23390 (.1 mg/kg) or the selective D-2 antagonist remoxipride (1.0 mg/kg), after which they received dihydrexidine (10 mg/kg) and were tested as above. The effects of dihydrexidine on social reactivity in mice of both lines were significantly antagonized by SCH-23390 but not attenuated by remoxipride. Antagonist pretreatment neither reinstated attack in the NC900 line nor nonagonistic approach behavior in the NC100 line, which suggests the importance of D-1/D-2 interactions to the initiation of action. These studies suggest an important role for D-1 dopamine receptors in the emotional response to social stimuli.