Hamlin Adam S, Clemens Kelly J, Choi Eun A, McNally Gavan P
School of Psychology, The University of New South Wales, Sydney, NSW, Australia.
Eur J Neurosci. 2009 Feb;29(4):802-12. doi: 10.1111/j.1460-9568.2009.06623.x. Epub 2009 Feb 5.
Paraventricular thalamus (PvTh) is uniquely placed to contribute to reinstatement of drug and reward seeking. It projects extensively to regions implicated in reinstatement including accumbens shell (AcbSh), prefrontal cortex (PFC) and basolateral amygdala (BLA), and receives afferents from other regions important for reinstatement such as lateral hypothalamus. We used complementary neuroanatomical and functional approaches to study the role of PvTh in context-induced reinstatement (renewal) of extinguished reward-seeking. Rats were trained to respond for a reward in context A, extinguished in context B and tested in context A or B. We applied the neuronal tracer cholera toxin B subunit (CTb) to AcbSh and examined retrograde-labelled neurons, c-Fos immunoreactivity (IR) and dual c-Fos/CTb labelled neurons in PvTh and other AcbSh afferents. In PvTh there was c-Fos IR in CTb-positive neurons associated with renewal showing activation of a PvTh-AcbSh pathway during renewal. In PFC there was little c-Fos IR in CTb-positive or negative neurons associated with renewal. In BLA, two distinct patterns of activation and retrograde labelling were observed. In rostral BLA there was significant c-Fos IR in CTb-negative neurons associated with renewal. In caudal BLA there was significant c-Fos IR in CTb-positive neurons associated with being tested in either the extinction (ABB) or training (ABA) context. We then studied the functional role of PvTh in renewal. Excitotoxic lesions of PvTh prevented renewal. These lesions had no effect on the acquisition of reward seeking. These results show that PvTh mediates context-induced reinstatement and that this renewal is associated with recruitment of a PvTh-AcbSh pathway.
室旁丘脑（PvTh）在促进药物复吸和奖赏寻求行为的恢复方面具有独特作用。它广泛投射到与复吸相关的区域，包括伏隔核壳（AcbSh）、前额叶皮质（PFC）和基底外侧杏仁核（BLA），并接收来自其他对复吸重要的区域（如下丘脑外侧）的传入神经。我们采用互补的神经解剖学和功能学方法，研究PvTh在情境诱导的消退奖赏寻求行为恢复（更新）中的作用。将大鼠训练在情境A中对奖赏做出反应，在情境B中消退，然后在情境A或B中进行测试。我们将神经元示踪剂霍乱毒素B亚基（CTb）应用于AcbSh，并检查室旁丘脑及其他AcbSh传入神经中逆行标记的神经元、c-Fos免疫反应性（IR）以及双c-Fos/CTb标记的神经元。在室旁丘脑中，与恢复相关的CTb阳性神经元中有c-Fos IR，表明在恢复过程中PvTh-AcbSh通路被激活。在前额叶皮质中，与恢复相关的CTb阳性或阴性神经元中几乎没有c-Fos IR。在基底外侧杏仁核中，观察到两种不同的激活和逆行标记模式。在杏仁核前部，与恢复相关的CTb阴性神经元中有显著的c-Fos IR。在杏仁核后部，在消退（ABB）或训练（ABA）情境中接受测试的CTb阳性神经元中有显著的c-Fos IR。然后我们研究了室旁丘脑在恢复中的功能作用。室旁丘脑的兴奋性毒性损伤阻止了恢复。这些损伤对奖赏寻求行为的习得没有影响。这些结果表明，室旁丘脑介导情境诱导的恢复，并且这种恢复与PvTh-AcbSh通路的募集有关。
