Background

Corticotropin-releasing factor (CRF) neural systems are important stress mechanisms in the central amygdala (CeA), bed nucleus of stria terminalis (BNST), nucleus accumbens (NAc), and related structures. CRF-containing neural systems are traditionally posited to generate aversive distress states that motivate overconsumption of rewards and relapse in addiction. However, CRF-containing systems may alternatively promote incentive motivation to increase reward pursuit and consumption without requiring aversive states.

Methods

We optogenetically stimulated CRF-expressing neurons in the CeA, BNST, or NAc using Crh-Cre+ rats (n = 37 female, n = 34 male) to investigate roles in incentive motivation versus aversive motivation. We paired CRF-expressing neuronal stimulations with earning sucrose rewards in two-choice and progressive ratio tasks and investigated recruitment of distributed limbic circuitry. We further assessed valence with CRF-containing neuron laser self-stimulation tasks.

Results

Channelrhodopsin excitation of CRF-containing neurons in the CeA and NAc amplified and focused incentive motivation and recruited activation of mesocorticolimbic reward circuitry. CRF systems in both the CeA and NAc supported laser self-stimulation, amplified incentive motivation for sucrose in a breakpoint test, and focused “wanting” on laser-paired sucrose over a sucrose alternative in a two-choice test. Conversely, stimulation of CRF-containing neurons in the BNST produced negative valence or aversive effects and recruited distress-related circuitry, as stimulation was avoided and suppressed motivation for sucrose.

Conclusions

CRF-containing systems in the NAc and CeA can promote reward consumption by increasing incentive motivation without involving aversion. In contrast, stimulation of CRF-containing systems in the BNST is aversive but suppresses sucrose reward pursuit and consumption rather than increase, as predicted by traditional hedonic self-medication hypotheses.

中文翻译：

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激活伏核、杏仁核和终纹床核中的促肾上腺皮质激素释放因子系统：激励动机还是厌恶动机？

 背景

促肾上腺皮质激素释放因子 (CRF) 神经系统是中央杏仁核 (CeA)、终纹床核 (BNST)、伏隔核 (NAc) 和相关结构的重要应激机制。传统上，含有 CRF 的神经系统被认为会产生厌恶的痛苦状态，从而激发过度消费奖励和成瘾复发。然而，包含 CRF 的系统也可以促进激励动机，以增加奖励追求和消费，而不需要厌恶状态。

 方法

我们使用Crh -Cre+ 大鼠（ n = 37 只雌性， n = 34 只雄性）对 CeA、BNST 或 NAc 中表达 CRF 的神经元进行光遗传学刺激，以研究激励动机与厌恶动机的作用。我们将表达 CRF 的神经元刺激与在两项选择和渐进比例任务中获得蔗糖奖励相结合，并研究了分布式边缘回路的招募。我们进一步评估了包含 CRF 的神经元激光自刺激任务的效价。

 结果

CeA 和 NAc 中含有 CRF 的神经元的视紫红质通道增强并集中了激励动机，并招募了中皮质边缘奖励回路的激活。 CeA 和 NAc 中的 CRF 系统都支持激光自刺激，在断点测试中放大了对蔗糖的激励动机，并在两项选择测试中将“想要”激光配对的蔗糖而不是蔗糖替代品。相反，刺激 BNST 中含有 CRF 的神经元会产生负价或厌恶效应，并招募与痛苦相关的电路，因为刺激被避免并抑制了对蔗糖的动机。

 结论

NAc 和 CeA 中包含 CRF 的系统可以通过增加激励动机来促进奖励消费，而不涉及厌恶。相比之下，对 BNST 中含有 CRF 的系统的刺激是令人厌恶的，但会抑制蔗糖奖励的追求和消耗，而不是像传统的享乐自我药疗假设所预测的那样增加。