Following the association of a neutral stimulus (conditioned stimulus, CS) with a biologically significant stimulus (unconditioned stimulus, US), CS-alone presentations generate extinction: a decline in the conditioned response. Many studies have revealed the neural substrates of fear extinction; however, a few have identified the brain regions responsible for appetitive extinction. Midbrain dopamine neurons are activated by presenting a reward or predictable reward cue, whereas the cue signaling the absence of reward activates the lateral habenula (LHb) neurons. We examined the engagement of the LHb in appetitive extinction. In the first phase, rats first received pairings of a CS (light) with US delivery (food pellets). In the second phase, rats in the CS-alone group underwent four CS-alone presentations, whereas those in the paired group received four pairings of light with food pellets. We also included a comparison group for CS-alone presentations: rats were placed in the training box without CS or US exposures in the first phase and received four CS-alone presentations in the second phase. Thirty minutes after the second phase, c-Fos levels in the ventral tegmental area (VTA), substantia nigra pars compacta (SNc), and LHb in these groups were measured. c-Fos levels in the LHb were higher in the paired-CS-alone group than in the paired-paired and comparison groups, while those in the VTA and SNc were significantly higher in the paired-paired group than in the other groups. On examination of LHb neurotoxic lesion effects on the decline of conditioned food-cup responses when a CS was repeatedly presented with no US, LHb lesions decelerated the decline in conditioned food-cup responses, suggesting a crucial role of LHb in appetitive extinction.

在中性刺激（条件刺激，CS）与具有生物学意义的刺激（无条件刺激，美国）相关联之后，单独的 CS 呈现会产生消退：条件反应的下降。许多研究揭示了恐惧消退的神经基础。然而，少数人已经确定了导致食欲消退的大脑区域。中脑多巴胺神经元通过呈现奖赏或可预测的奖赏线索被激活，而表明没有奖赏的线索激活外侧缰核 (LHb) 神经元。我们检查了 LHb 在食欲消退中的作用。在第一阶段，大鼠首先接受 CS（光）与 US 递送（食物颗粒）的配对。在第二阶段，单独 CS 组的大鼠经历了四次单独 CS 演示，而配对组中的那些接受了四对带有食物颗粒的光。我们还包括一个单独 CS 演示的对照组：在第一阶段将大鼠放置在没有 CS 或 US 暴露的训练箱中，并在第二阶段接受四个单独的 CS 演示。第二阶段后 30 分钟，测量了这些组中腹侧被盖区 (VTA)、黑质致密部 (SNc) 和 LHb 中的 c-Fos 水平。LHb 中的 c-Fos 水平在单独 CS 组中高于配对组和对照组，而 VTA 和 第二阶段后 30 分钟，测量了这些组中腹侧被盖区 (VTA)、黑质致密部 (SNc) 和 LHb 中的 c-Fos 水平。LHb 中的 c-Fos 水平在单独 CS 组中高于配对组和对照组，而 VTA 和 第二阶段后 30 分钟，测量了这些组中腹侧被盖区 (VTA)、黑质致密部 (SNc) 和 LHb 中的 c-Fos 水平。LHb 中的 c-Fos 水平在单独 CS 组中高于配对组和对照组，而 VTA 和配对组的 SNc 显着高于其他组。在检查 LHb 神经毒性损伤对 CS 在没有 US 的情况下反复呈现时条件性食物杯反应下降的影响时，LHb 损伤减缓了条件性食物杯反应的下降，这表明 LHb 在食欲消退中的关键作用。