Department of Psychology and Neuroscience Program, Temple University, Philadelphia, PA, 19122, USA.
Department of Psychology and Neuroscience Program, Temple University, Philadelphia, PA, 19122, USA.
Neurosci Biobehav Rev. 2020 Dec;119:86-100. doi: 10.1016/j.neubiorev.2020.09.014. Epub 2020 Oct 3.
Motivated behaviors are controlled by the mesocorticolimbic dopamine (DA) system, consisting of projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and prefrontal cortex (PFC), with input from structures including the medial preoptic area (mPOA). Sex differences are present in this circuit, and gonadal hormones (e.g., estradiol and testosterone) are important for regulating DA transmission. Early life stress (ELS) also regulates the mesocorticolimbic DA system. ELS modifies motivated behaviors and the underlying DA circuitry, increasing risk for disorders such as substance use disorder, major depression, and schizophrenia. ELS has been shown to change gonadal hormone signaling in both sexes. Thus, one way that ELS could impact mesocorticolimbic DA is by altering the efficacy of gonadal hormones. This review provides evidence for this idea by integrating the gonadal hormone, motivation, and ELS literature to argue that ELS alters gonadal hormone signaling to impact motivated behavior. We also discuss the importance of these effects in the context of understanding risk and treatments for psychiatric disorders in men and women.
动机行为受中脑边缘多巴胺 (DA) 系统控制，该系统由腹侧被盖区 (VTA) 向伏隔核 (NAc) 和前额叶皮层 (PFC) 的投射组成，其输入来自包括内侧视前区 (mPOA) 在内的结构。该回路存在性别差异，性腺激素（例如雌激素和睾酮）对于调节 DA 传递很重要。早期生活应激 (ELS) 也调节中脑边缘 DA 系统。ELS 改变动机行为和潜在的 DA 回路，增加物质使用障碍、重度抑郁症和精神分裂症等疾病的风险。ELS 已被证明会改变两性的性腺激素信号。因此，ELS 影响中脑边缘 DA 的一种方式可能是通过改变性腺激素的功效。通过整合性腺激素、动机和 ELS 文献，本综述提供了这一观点的证据，认为 ELS 改变了性腺激素信号，从而影响了动机行为。我们还讨论了这些影响在理解男性和女性精神疾病风险和治疗中的重要性。
