中脑边缘多巴胺系统、杏仁核和终纹床核中的促肾上腺皮质释放因子系统：激励动机还是厌恶动机？
Activating Corticotropin-Releasing Factor Systems in the Nucleus Accumbens, Amygdala, and Bed Nucleus of Stria Terminalis: Incentive Motivation or Aversive Motivation?
机构信息
Department of Psychology, University of Michigan, Ann Arbor, Michigan.
Department of Neuroscience, Georgetown University, Washington, DC.
出版信息
Biol Psychiatry. 2021 Jun 15;89(12):1162-1175. doi: 10.1016/j.biopsych.2021.01.007. Epub 2021 Jan 21.
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.
背景
促肾上腺皮质释放因子 (CRF) 神经网络系统是中枢杏仁核 (CeA)、终纹床核 (BNST)、伏隔核 (NAc) 及相关结构中的重要应激机制。传统上认为，含有 CRF 的神经网络系统会产生令人痛苦的不适状态，从而促使过度消费奖励并导致成瘾复发。然而，含有 CRF 的系统也可能会促进激励动机，增加对奖励的追求和消费，而无需产生不适状态。
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 中的 CRF 表达神经元进行光遗传刺激，以研究其在激励动机与厌恶动机中的作用。我们将 CRF 表达神经元的刺激与在双选择和渐进比例任务中获得蔗糖奖励相配对，并研究了分布式边缘电路的募集情况。我们进一步通过含有 CRF 的神经元激光自我刺激任务来评估效价。
结果
CeA 和 NAc 中 CRF 表达神经元的通道视紫红质激发放大了激励动机，并聚焦了中脑边缘奖励回路的激活。CeA 和 NAc 中的 CRF 系统均支持激光自我刺激，在断点测试中放大了对蔗糖的激励动机，并在双选择测试中，将“渴望”聚焦在激光配对的蔗糖上，而不是蔗糖替代品上。相反，BNST 中 CRF 表达神经元的刺激会产生负效价或厌恶效应，并募集与痛苦相关的回路，因为刺激会被避免并抑制对蔗糖的动机。
结论
NAc 和 CeA 中的 CRF 系统可以通过增加激励动机来促进奖励消费，而不会涉及厌恶。相比之下，BNST 中 CRF 系统的刺激是厌恶的，但会抑制而不是增加蔗糖奖励的追求和消费，这与传统的享乐自我药物治疗假说预测的相反。
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