Instituto de Neurociências & Comportamento and Laboratório de Neuropsicofarmacologia, FFCLRP, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Int J Neuropsychopharmacol. 2013 Jun;16(5):1045-57. doi: 10.1017/S146114571200082X. Epub 2012 Sep 11.
Although dopamine-related circuits are best known for their roles in appetitive motivation, consistent data have implicated this catecholamine in some forms of response to stressful situations. In fact, projection areas of the ventral tegmental area, such as the amygdala and hippocampus, are well established to be involved in the acquisition and expression of fear conditioning, while less is known about the role of the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) in these processes. In the present study, we initially investigated the involvement of the mPFC and NAc in the expression of conditioned fear, assessing freezing behaviour and Fos protein expression in the brains of rats exposed to a context, light or tone previously paired with footshocks. Contextual and cued stimuli were able to increase the time of the freezing response while only the contextual fear promoted a significant increase in Fos protein expression in the mPFC and caudal NAc. We then examined the effects of specific dopaminergic agonists and antagonists injected bilaterally into the posterior medioventral shell subregion of the NAc (NAcSh) on the expression of contextual fear. SKF38393, quinpirole and sulpiride induced no behavioural changes, but the D1-like receptor antagonist SCH23390 increased the freezing response of the rats and selectively reduced Fos protein expression in the anterior cingulate cortex and rostral NAcSh. These findings confirm the involvement of the NAcSh in the expression of contextual fear memories and indicate the selective role of NAcSh D1-like receptors and anterior cingulate cortex in this process.
尽管多巴胺相关回路以其在食欲动机中的作用而闻名,但一致的数据表明这种儿茶酚胺在某些形式的应激反应中起作用。事实上,腹侧被盖区的投射区域,如杏仁核和海马体,已被证实参与了恐惧条件反射的获得和表达,而对于内侧前额叶皮层(mPFC)和伏隔核(NAc)在这些过程中的作用知之甚少。在本研究中,我们最初研究了 mPFC 和 NAc 在条件性恐惧表达中的作用,评估了暴露于先前与电击配对的环境、光或音的大鼠的冻结行为和脑中的 Fos 蛋白表达。上下文和线索刺激能够增加冻结反应的时间,而只有上下文恐惧会导致 mPFC 和尾侧 NAc 中的 Fos 蛋白表达显著增加。然后,我们检查了双侧注射到 NAc 的后 Medioventral 壳区(NAcSh)的特定多巴胺激动剂和拮抗剂对上下文恐惧表达的影响。SKF38393、喹吡罗和舒必利没有引起行为变化,但 D1 样受体拮抗剂 SCH23390 增加了大鼠的冻结反应,并选择性地降低了前扣带皮层和前侧 NAcSh 中的 Fos 蛋白表达。这些发现证实了 NAcSh 在表达上下文恐惧记忆中的作用,并表明 NAcSh D1 样受体和前扣带皮层在这个过程中的选择性作用。