Olmedo-Córdoba Manuela, Prados-Pardo Angeles, Martín-González Elena, Moreno-Montoya Margarita
Department of Psychology, Clinical and Experimental, Neuroscience Research Group CTS280 and CIBIS (Centro de Investigación Para El Bienestar y La Inclusión Social) Research Center, University of Almería, Ctra. Sacramento, S/N, 04120, Almería, Spain.
Área de Psicobiología, Facultat de Ciències de la Salut, Universitat Jaume I, Castellón de la Plana, Spain.
Mol Neurobiol. 2025 Jul 23. doi: 10.1007/s12035-025-05218-4.
Compulsive behavior is a potential transdiagnostic symptom highly present in different neuropsychiatric disorders, including obsessive-compulsive disorder (OCD), anxiety, schizophrenia, and addiction. Transcranial direct current stimulation (tDCS), a non-invasive neurostimulation technique, has been proposed as an effective and safe therapeutic strategy for reducing compulsive behavior. However, its underlying molecular mechanisms remain unclear. In the present study, we assessed whether anodal tDCS treatment reduces compulsivity through neuroplasticity mechanisms in male Wistar rats selected by high compulsive drinking on schedule-induced polydipsia (SIP). Compulsive rats received low-intensity direct current stimulation (0.5 mA) over the frontal cortex (FC) once a day for 8 consecutive days for 20 min, compared to a sham group without stimulation. tDCS treatment did not induce a significant reduction in compulsivity on SIP. However, RT-qPCR analyses revealed that tDCS led to a significant increase in different neuroplasticity markers, such as Htr2a, Grin1, Bdnf, Ngf, and Scn2a in the FC of compulsive rats compared to sham treatment. In contrast, tDCS treatment did not induce any change in the neuroplasticity markers in the amygdala. These data suggest that tDCS might be able to induce neuromodulation in the FC by an increase in neuroplasticity gene expression, despite not observing significant differences in compulsive behavior on SIP. Our findings also suggest that future studies employing neuromodulation techniques should aim to target neuroplastic changes within the amygdala, with the potential to reduce compulsive behaviors.
强迫行为是一种潜在的跨诊断症状，在不同的神经精神疾病中高度存在，包括强迫症（OCD）、焦虑症、精神分裂症和成瘾症。经颅直流电刺激（tDCS）是一种非侵入性神经刺激技术，已被提议作为减少强迫行为的有效且安全的治疗策略。然而，其潜在的分子机制仍不清楚。在本研究中，我们评估了在按计划诱导多饮（SIP）实验中通过高强迫性饮水筛选出的雄性Wistar大鼠中，阳极tDCS治疗是否通过神经可塑性机制降低强迫性。与未接受刺激的假手术组相比，强迫性大鼠连续8天每天在额叶皮质（FC）接受一次低强度直流电刺激（0.5 mA），持续20分钟。tDCS治疗并未导致SIP实验中强迫性的显著降低。然而，逆转录-定量聚合酶链反应（RT-qPCR）分析显示，与假手术治疗相比，tDCS导致强迫性大鼠FC中不同神经可塑性标志物（如Htr2a、Grin1、Bdnf、Ngf和Scn2a）显著增加。相反，tDCS治疗未引起杏仁核中神经可塑性标志物的任何变化。这些数据表明，尽管在SIP实验中未观察到强迫行为的显著差异，但tDCS可能通过增加神经可塑性基因表达在FC中诱导神经调节。我们的研究结果还表明，未来采用神经调节技术的研究应旨在针对杏仁核内的神经可塑性变化，有可能减少强迫行为。
