A feature in the pathophysiology of major depressive disorder (MDD), a mood disorder, is the impairment of excitatory synapses in the prefrontal cortex. Intriguingly, different types of treatment with fairly rapid antidepressant effects (within days or a few weeks), such as ketamine, electroconvulsive therapy and non-invasive neurostimulation, seem to converge on enhancement of neural plasticity. However, the forms and mechanisms of plasticity that link antidepressant interventions to the restoration of excitatory synaptic function are still unknown. In this Review, we highlight preclinical research from the past 15 years showing that ketamine and psychedelic drugs can trigger the growth of dendritic spines in cortical pyramidal neurons. We compare the longitudinal effects of various psychoactive drugs on neuronal rewiring, and we highlight rapid onset and sustained time course as notable characteristics for putative rapid-acting antidepressant drugs. Furthermore, we consider gaps in the current understanding of drug-evoked in vivo structural plasticity. We also discuss the prospects of using synaptic remodelling to understand other antidepressant interventions, such as repetitive transcranial magnetic stimulation. Finally, we conclude that structural neural plasticity can provide unique insights into the neurobiological actions of psychoactive drugs and antidepressant interventions.

重度抑郁症 （MDD） 是一种情绪障碍，其病理生理学的一个特征是前额叶皮层兴奋性突触受损。有趣的是，具有相当快速的抗抑郁作用（在几天或几周内）的不同类型的治疗方法，如氯胺酮、电休克疗法和非侵入性神经刺激，似乎都集中在增强神经可塑性上。然而，将抗抑郁药干预与兴奋性突触功能恢复联系起来的可塑性形式和机制仍然未知。在这篇综述中，我们重点介绍了过去 15 年的临床前研究表明，氯胺酮和迷幻药可以触发皮质锥体神经元树突棘的生长。我们比较了各种精神活性药物对神经元再布线的纵向影响，并强调了快速起效和持续时间进程是推定的快速起效抗抑郁药物的显着特征。此外，我们考虑了当前对药物诱发的体内结构可塑性的理解差距。我们还讨论了使用突触重塑来了解其他抗抑郁干预措施的前景，例如重复经颅磁刺激。最后，我们得出结论，结构神经可塑性可以为精神活性药物和抗抑郁药干预的神经生物学作用提供独特的见解。