Fadok Jonathan P, Dickerson Tavis M K, Palmiter Richard D
Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, Washington 98195, USA.
J Neurosci. 2009 Sep 9;29(36):11089-97. doi: 10.1523/JNEUROSCI.1616-09.2009.
Dopamine (DA) is implicated in many behaviors, including motor function, cognition, and reward processing; however, the role of DA in fear processing remains equivocal. To examine the role of DA in fear-related learning, dopamine-deficient (DD) mice were tested in a fear-potentiated startle paradigm. DA synthesis can be restored in DD mice through administration of 3, 4-dihydroxy-l-phenylalanine (l-Dopa), thereby permitting the assessment of fear processing in either a DA-depleted or -replete state. Fear-potentiated startle was absent in DD mice but could be restored by l-Dopa administration immediately after fear conditioning. Selective viral-mediated restoration of DA synthesis within the ventral tegmental area fully restored fear learning in DD mice, and restoration of DA synthesis to DA neurons projecting to the basolateral amygdala restored short-term memory but not long-term memory or shock sensitization. We also demonstrate that the DA D(1) receptor (D(1)R) and D(2)-like receptors are necessary for cue-dependent fear learning. These findings indicate that DA acting on multiple receptor subtypes within multiple target regions facilitates the stabilization of fear memory.
多巴胺(DA)与许多行为有关,包括运动功能、认知和奖赏处理;然而,DA在恐惧处理中的作用仍不明确。为了研究DA在恐惧相关学习中的作用,对多巴胺缺乏(DD)小鼠进行了恐惧增强惊吓范式测试。通过给予3,4-二羟基-L-苯丙氨酸(L-多巴),可以恢复DD小鼠的DA合成,从而能够评估在DA缺乏或充足状态下的恐惧处理情况。DD小鼠不存在恐惧增强惊吓,但在恐惧条件反射后立即给予L-多巴可恢复。腹侧被盖区内DA合成的选择性病毒介导恢复完全恢复了DD小鼠的恐惧学习,并且向基底外侧杏仁核投射的DA神经元的DA合成恢复可恢复短期记忆,但不能恢复长期记忆或惊吓敏化。我们还证明,DA D(1)受体(D(1)R)和D(2)样受体对于线索依赖性恐惧学习是必需的。这些发现表明,作用于多个靶区域内多个受体亚型的DA促进了恐惧记忆的稳定。