Department of Psychology, Yale University, New Haven, Connecticut 06520
Department of Psychology, Yale University, New Haven, Connecticut 06520.
J Neurosci. 2022 Jan 26;42(4):670-681. doi: 10.1523/JNEUROSCI.0413-21.2021. Epub 2021 Dec 3.
To competently navigate the world, individuals must flexibly balance distinct aspects of social gaze, orienting toward others and inhibiting orienting responses, depending on the context. These behaviors are often disrupted amongst patient populations treated with serotonergic drugs. However, those in the field lack a clear understanding of how the serotonergic system mediates social orienting and inhibiting behaviors. Here, we tested how increasing central concentrations of serotonin with the direct precursor 5-hydroxytryptophan (5-HTP) would modulate the ability of rhesus macaques (both sexes) to use eye movements to flexibly orient to, or inhibit orienting to, faces. Systemic administrations of 5-HTP effectively increased central serotonin levels and impaired flexible orientation and inhibition. Critically, 5-HTP selectively impaired the ability of monkeys to inhibit orienting to face images, whereas it similarly impaired orienting to face and control images. 5-HTP also caused monkeys to perseverate on their gaze responses, making them worse at flexibly switching between orienting and inhibiting behaviors. Furthermore, the effects of 5-HTP on performance correlated with a constriction of the pupil, an increased time to initiate trials, and an increased reaction time, suggesting that the disruptive effects of 5-HTP on social gaze behaviors are likely driven by a downregulation of arousal and motivational states. Together, these findings provide causal evidence for a modulatory relationship between 5-HTP and social gaze behaviors in nonhuman primates and offer translational insights for the role of the serotonergic system in social gaze. Behavioral changes arising from pharmacological agents that target serotonergic functions are complex and difficult to predict. Here, we examined the causal impacts of administering the direct precursor of serotonin, 5-HTP, on orienting and inhibiting social gaze in nonhuman primates. 5-HTP increased central concentrations of serotonin and selectively impaired the ability of monkeys to inhibit orienting to faces while similarly impairing the ability of monkeys to orient to face and control images. These behavioral gaze impairments were systematically associated with a downregulation of arousal and motivational states, indexed by pupil constriction, increased time to initiate trials, and increased reaction time. These findings provide a causal link between 5-HTP and social gaze behaviors in nonhuman primates and provide translational insights about serotonergic interventions.
为了能够熟练地适应这个世界，个体必须根据情境灵活地平衡社交注视的不同方面，既要关注他人，又要抑制自身的定向反应。而在接受血清素能药物治疗的患者群体中，这些行为通常会受到干扰。然而，该领域的研究人员对于血清素系统如何介导社交定向和抑制行为知之甚少。在这里，我们通过测试直接前体 5-羟色氨酸（5-HTP）增加中枢血清素浓度会如何调节恒河猴（雌雄两性）使用眼球运动灵活地转向或抑制转向面部的能力，来研究这个问题。5-HTP 的系统性给药有效地增加了中枢血清素水平，并损害了灵活定向和抑制能力。关键的是，5-HTP 选择性地损害了猴子抑制转向面部图像的能力，而对转向面部和控制图像的能力则有类似的损害。5-HTP 还导致猴子在注视反应上持续存在，使其在灵活地在定向和抑制行为之间切换时表现更差。此外，5-HTP 对表现的影响与瞳孔收缩、试验启动时间增加和反应时间增加相关，这表明 5-HTP 对社交注视行为的破坏作用可能是由唤醒和动机状态的下调驱动的。综上所述，这些发现为非人类灵长类动物 5-HTP 与社交注视行为之间的调节关系提供了因果证据，并为血清素系统在社交注视中的作用提供了转化见解。靶向血清素功能的药物对行为的影响是复杂且难以预测的。在这里，我们研究了直接前体 5-HTP 给药对非人类灵长类动物定向和抑制社交注视的因果影响。5-HTP 增加了中枢血清素浓度，并选择性地损害了猴子抑制转向面部的能力，同时也损害了猴子转向面部和控制图像的能力。这些行为性注视障碍与唤醒和动机状态的下调系统相关，表现为瞳孔收缩、试验启动时间增加和反应时间增加。这些发现为非人类灵长类动物 5-HTP 与社交注视行为之间提供了因果联系，并提供了关于血清素干预的转化见解。
