Nasehi Mohammad, Hajian Maryam, Ebrahimi-Ghiri Mohaddeseh, Zarrindast Mohammad-Reza
Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Northern Branch, Tehran, Iran.
Psychopharmacology (Berl). 2016 Jan;233(2):213-24. doi: 10.1007/s00213-015-4096-6. Epub 2015 Nov 7.
There is much evidence suggesting that the mesoamygdala dopaminergic (DAergic) system plays a crucial role in the formation and expression of fear conditioning, with both D1 and D2 receptors being involved. In addition, cannabinoid CB1 receptor (CB1R) signaling modulates DAergic pathways. The present study sought to determine the involvement of basolateral amygdala (BLA) dopamine receptors in arachidonylcyclopropylamide (ACPA)-induced fear learning deficits. Context- and tone-dependent fear conditioning in adult male NMRI mice was evaluated. Pre-training intraperitoneal administration of ACPA (0.1 mg/kg) decreased the percentage of freezing in context- or tone-dependent fear conditioning, suggesting an acquisition impairment. Pre-training intra-BLA microinjection of a subthreshold dose of SKF38393 (D1-like receptor agonist), SCH23390 (D1-like receptor antagonist), quinpirole (D2-like receptor agonist), or sulpiride (D2-like receptor antagonist) did not alter the context-dependent fear learning deficit induced by ACPA, while SKF38393 or quinpirole restored ACPA effect on tone-dependent fear learning. Moreover, SKF38393 (1 μg/mouse), SCH23390 (0.04 and 0.08 μg/mouse), or quinpirole (0.1 μg/mouse) all impaired context-dependent fear learning. It is concluded that D1 or D2 dopamine (DA) receptor activation restores tone- but not context-dependent fear learning deficit induced by CB1 activation using ACPA.
有许多证据表明，中杏仁核多巴胺能（DAergic）系统在恐惧条件反射的形成和表达中起关键作用，D1和D2受体均参与其中。此外，大麻素CB1受体（CB1R）信号传导调节多巴胺能通路。本研究旨在确定基底外侧杏仁核（BLA）多巴胺受体在花生四烯酰环丙酰胺（ACPA）诱导的恐惧学习缺陷中的作用。评估成年雄性NMRI小鼠的情境和音调依赖性恐惧条件反射。训练前腹腔注射ACPA（0.1mg/kg）可降低情境或音调依赖性恐惧条件反射中的僵住百分比，表明存在习得障碍。训练前在BLA内微量注射阈下剂量的SKF38393（D1样受体激动剂）、SCH23390（D1样受体拮抗剂）、喹吡罗（D2样受体激动剂）或舒必利（D2样受体拮抗剂），并未改变ACPA诱导的情境依赖性恐惧学习缺陷，而SKF38393或喹吡罗恢复了ACPA对音调依赖性恐惧学习的影响。此外，SKF38393（1μg/小鼠）、SCH23390（0.04和0.08μg/小鼠）或喹吡罗（0.1μg/小鼠）均损害情境依赖性恐惧学习。结论是，D1或D2多巴胺（DA）受体激活可恢复由ACPA激活CB1诱导的音调依赖性而非情境依赖性恐惧学习缺陷。
