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

**Authors:** Manuela Olmedo-Córdoba, Angeles Prados-Pardo, Elena Martín-González, Margarita Moreno-Montoya

PMC · DOI: 10.1007/s12035-025-05218-4 · 2025-07-23

## TL;DR

This study explores how tDCS affects compulsive behavior and brain plasticity in rats, finding increased neuroplasticity in the frontal cortex but no change in compulsive drinking.

## Contribution

The study reveals that tDCS increases neuroplasticity gene expression in the frontal cortex of compulsive rats, despite no behavioral change.

## Key findings

- tDCS increased neuroplasticity markers like Htr2a, Grin1, Bdnf, Ngf, and Scn2a in the frontal cortex of compulsive rats.
- tDCS did not reduce compulsive drinking behavior in the schedule-induced polydipsia test.
- No changes in neuroplasticity markers were observed in the amygdala after tDCS treatment.

## Abstract

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.

## Linked entities

- **Genes:** HTR2A (5-hydroxytryptamine receptor 2A) [NCBI Gene 3356], GRIN1 (glutamate ionotropic receptor NMDA type subunit 1) [NCBI Gene 2902], BDNF (brain derived neurotrophic factor) [NCBI Gene 627], NGF (nerve growth factor) [NCBI Gene 4803], SCN2A (sodium voltage-gated channel alpha subunit 2) [NCBI Gene 6326]
- **Diseases:** obsessive–compulsive disorder (MONDO:0008114), anxiety (MONDO:0005618), schizophrenia (MONDO:0005090)

## Full-text entities

- **Genes:** Bdnf (brain-derived neurotrophic factor) [NCBI Gene 24225], Grin1 (glutamate ionotropic receptor NMDA type subunit 1) [NCBI Gene 24408] {aka GluN1, NMDAR1, NR1}, Htr2a (5-hydroxytryptamine receptor 2A) [NCBI Gene 29595] {aka 5-HT2A, 5Ht-2}, Scn2a (sodium voltage-gated channel alpha subunit 2) [NCBI Gene 24766] {aka NachII, Nav1.2, RII/RIIA, RNSCPIIR, SCN, Scn2a1}, Ngf (nerve growth factor) [NCBI Gene 310738] {aka Ngfb, beta-NGF}
- **Diseases:** anxiety (MESH:D001007), addiction (MESH:D019966), Compulsive Behavior (MESH:D003193), Compulsive (MESH:D000073932), OCD (MESH:D009771), compulsive drinking (MESH:D063425), SIP (MESH:D059606), schizophrenia (MESH:D012559), neuropsychiatric disorders (MESH:D001523)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12559075/full.md

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Source: https://tomesphere.com/paper/PMC12559075