Increased Neuroplasticity in Frontal Cortex to Reduce Compulsive Behavior: A Preclinical tDCS Study in Male Rats

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.