Selective antagonism of medial prefrontal cortex D4 receptors decreases fear-related behaviour in rats
Selective antagonism of medial prefrontal cortex D4 receptors decreases fear-related behaviour in rats
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DOI：
10.1111/j.0953-816x.2004.03447.x
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发表时间：
2004-06-01
影响因子：
3.4
通讯作者：
Treit, D
中科院分区：
文献类型：
--
作者：
Shah, AA;Sjovold, T;Treit, D
众所周知，中脑边缘皮质多巴胺通路在压力和恐惧期间高度活跃。然而，很少有研究直接研究这一途径中的多巴胺受体如何影响与恐惧相关的行为。本研究探讨了选择性拮抗内侧前额叶皮层（MPFC）D-4、D-1和D-2多巴胺受体对大鼠高架十字迷宫和电击探针埋藏实验中恐惧行为的影响。结果表明，双侧MPFC内输注高选择性D-4拮抗剂L-745 870（0.2、1或10 nmol/0.5穆尔）可增加高架十字迷宫试验中的开臂进入百分比和开臂时间（1 nmol/0.5穆尔），并减少电击探针试验中的埋藏持续时间（0.2或1 nmol/0.5穆尔）。此外，D-4拮抗剂的剂量均不影响一般活动或疼痛敏感性的测量。MPFC内输注D-1拮抗剂SCH-23390（0.2或1 nmol/0.5穆尔）或D-2拮抗剂瑞莫西必利（0.2、1或10 nmol/0.5穆尔）在两项试验中均无显著行为效应。总之，这些发现表明MPFC D-4受体可能在介导恐惧相关行为中发挥重要作用。
It is well known that the mesolimbocortical dopamine pathway is highly active during periods of stress and fear. However, very little research has directly examined how dopamine receptors in this pathway influence fear-related behaviour. The present study examined the effects of selective antagonism of D-4, D-1 and D-2 dopamine receptors of the medial prefrontal cortex (MPFC) on rats' fear behaviour in the elevated plus-maze and the shock-probe burying tests. The results demonstrated that bilateral intra-MPFC infusions of the highly selective D-4 antagonist, L-745 870 (0.2, 1 or 10 nmol/0.5 muL), increased the percentage of open-arm entries and open-arm time in the elevated plus-maze test (1 nmol/0.5 muL), and decreased the duration of burying in the shock-probe test (0.2 or 1 nmol/0.5 muL). Furthermore, none of the doses of the D-4 antagonist affected measures of general activity or pain sensitivity. Intra-MPFC infusions of the D-1 antagonist, SCH-23390 (0.2 or 1 nmol/0.5 muL), or the D-2 antagonist, remoxipride (0.2, 1 or 10 nmol/0.5 muL), had no significant behavioural effects in either test. Taken together, these findings suggest that MPFC D-4 receptors may play an important role in the mediation of fear-related behaviour.