Table 1.
Summary of tDCS Studies Conducted in Normal Animals and Animal Models of Disease
| References | Species | Gender | Age and/or Weight | Disease models | Areas of stimulation | Charge density (A/m2) | Number of days x sessions/day | Results/observations |
|---|---|---|---|---|---|---|---|---|
| Liebetanz et al., 2006a | Wistar rats | M | 332–422 g | Cortical spreading depression | Unilateral parietal cortex | 28.50 | 1 x 1 | Anodal tDCS increases CSD spreading velocity. |
| Liebetanz et al., 2006b | Wistar rats | M | 245–309 g | Epilepsy | Unilateral parietal cortex | 28.57 or 57.14 | 1 x 1 | Cathodal tDCS shows anticonvulsive properties. |
| Fregni and Pascual- Leone, 2007 | Wistar rats | M | 358–373 g | Cortical spreading depression | Unilateral parietal cortex | 28.5 | 1 x 1 | Anodal tDCS increases CSD spreading velocity preconditioned by 1-Hz repetitive electrical stimulations. |
| Schweid et al., 2008 | Cats | M | 2.9–3.2 kg | - | Unilateral visuoparietal cortex | 5 | 1 x 1 | Cathodal tDCS induces decreased performance for static visual targets presented in the contrastimulated visual hemifield. |
| Ben Taib and Manto, 2009 | Sprague-Dawley rats | M | 280–400 g | Hemi-cerebellectomy | Unilateral motor cortex | 51.20 | 1 x 1 | Anodal tDCS antagonizes motor cortex hypoexcitability induced by high-frequency stimulation of the interpositus nucleus. |
| Liebetanz et al., 2009 | Wistar rats | M&F | 286–334 g | - | Unilateral frontal cortex | 0.286 to 285.7 | 1 x 1 | Threshold for tissue damage using cathodal tDCS established at 142.9 A/m2. |
| Kim et al., 2010 | Sprague-Dawley rats | NS | 5 wk | Ischemia (unilateral MCAO) | Unilateral visual cortex | 1.26 | 14 x 1 | Anodal tDCS have neuroprotective effects on neural axons following infarct. |
| Cambiaghi et al., 2010 | C57BL/6 mice | F | 10–14wk/ 25–30 g | - | Unilateral primary motor cortex | 55.50 | 1 x 1 | Anodal tDCS increases motor evoked potential. Cathodal tDCS decreases it. |
| Wachter et al., 2011 | Sprague-Dawley rats | M | ~310 g | - | Unilateral middle cerebral artery territory | 7.14, 14.29, or 28.57 | 1 x 1 | Anodal tDCS increases cerebral blood flow. Cathodal tDCS decreases it. Higher current density results in more distinct effects. |
| Takano et al., 2011 | Sprague-Dawley rats | M | ~288 g | - | Bilateral frontal cortex (with electrode placement on the midline) | 1.60 and 16 | 1 x 1 | Anodal tDCS increases fMRI signal intensity in the frontal cortex and nucleus. accumbens. |
| Cambiaghi et al., 2011 | C57BL/6 mice | F | 8–12 wk | - | Unilateral primary motor cortex | 55.50 | 1 x 1 | Increase (anodal) or decrease (cathodal) in size of visual evoked potentials for 10min after tDCS. |
| Dockery et al., 2011 | Long-Evans rats | M | 250–325 g | - | Unilateral frontal cortex | 57.14 | 1 x 1 | Long-term benefits of frontal cathodal tDCS when paired with training on working memory and skill learning of a novel task. |
| Kamida et al., 2011 | Wistar rats | M | 23 d | Epilepsy | Unilateral motor cortex | 57.10 | 14 x 1 | Anodal tDCS has neuroprotective effects on hippocampal cells and reduces the granular and CA3 mossy fiber sprouting. Further reduces convulsions and rescues cognitive impairments. |
| Li et al., 2011b | Sprague-Dawley rats | F | NS | Parkinson’s disease (unilateral 6-OHDA lesion) | Unilateral primary motor cortex | 11.43 or 22.86 | 1 x 1 | Anodal tDCS abolishes the ipsilateral bias in a corridor test (effect of 1 d). |
| Yoon et al., 2012 | Sprague-Dawley rats | M | 6wk/220– 280 g | Ischemia (unilateral MCAO) | Unilateral at ischemic borders (established by MRI) | 28.20 | 5 x 1 | Anodal tDCS increases MAP-2 and GAP-43 staining in both lesioned and intact brain. |
| Marquez-Ruiz et al., 2012 | New Zealand white albino rabbits | NS | 2.3–2.7 kg | - | Unilateral somatosensory cortex | 3.70 | 1 x 1 | Anodal tDCS increases evoked potential. Cathodal tDCS decreases it. Lasting effects are observed only after cathodal tDCS. Both types of stimulation modify thalamo-cortical synapses at the presynaptic site. tDCS modulates the sensory perception process of associative learning. A1R activation are necessary for cathodal-evoked LTD. |
| Spezia Adachi et al., 2012 | Wistar rats | M | 250–300 g | Chronic inflammation (intraplantar injections of CFA) | Bilateral parietal cortex | 33.40 | 8 x 1 | Anodal tDCS has antinociceptive properties. |
| Rueger et al., 2012 | Wistar rats | M | 290–330 g | - | Unilateral motor cortex | 142.90 | 5 x 1 or 10 x 1 | Anodal and cathodal tDCS increase the number of Iba1+ cells. Cathodal tDCS increases the number of proliferating cells and He3+ neural stem cells in the cortex. |
| Jiang et al., 2012 | Wistar rats | M | 4–5 mo | Ischemia (unilateral MCAO) | Unilateral visual cortex | 1.26 | (3.7 or 14) x 1 | Anodal tDCS improves motor functions. Increased density of dendritic spines and decreased pannexin-1 mRNA levels. |
| Spezia Adachi et al., 2012 | Sprague-Dawley rats | M | 60 d/180– 230 g | Chronic stress-induced pain | Bilateral parietal cortex (with electrode placement on the midline) | 33.40 | 8 x 1 | Anodal tDCS has antinociceptive effects and reduces TNF-α level in the hippocampus (serum levels unchanged). |
| Zobeiri and van Luijtelaar, 2013 | WAG/Rij rats | M | 6 mo/322– 364 g | Genetic model of absence epilepsy | Bilateral perioral region of the somatosensory cortex (use of 2 independent electrodes) | 28.57 and 42.86 | 1 x 4 | Reduced number of slow-wave discharges during and after cathodal tDCS. Increased sub-delta and delta waves in the motor cortex suggest the hyperpolarization of cortical cells. |
| Tanaka et al., 2013 | Sprague-Dawley rats | M | 9 wk | - | Bilateral frontal cortex (with electrode placement on the midline) | 32 | 1 x 1 | Cathodal, but not anodal stimulation, increases extracellular striatal dopamine levels. |
| Bolzoni et al., 2013b | Cats | NS | 2.2–3.4 kg | - | Unilateral sensorimotor cortex | 1 or 2.50 | 1 x several | Anodal tDCS facilitates the activation of rubrospinal and reticulospinal neurons. |
| Bolzoni et al., 2013a | Sprague Dawley & Wistar rats | M&F | 200–300 g | - | Unilateral sensorimotor cortex | 4.16 | 1 x (5 to 7) | Firing of subcortical structures (medial longitudinal fascicle and red nucleus) is facilitated by cathodal tDCS and depressed by anodal tDCS. |
| Peruzzotti- Jametti et al., 2013 | C57/BL6 mice | M | 8–10wk/ 20–22 g | Ischemia (unilateral MCAO) | Left parietal area | 55.0 | 1 x 2 | Cathodal tDCS decreases the number of Iba+ and CD45+ cells at the infarct site, reduces the infarct size, decreases the number of caspase-3+ cells in the cortex and striatum, and reduces glutamate and NR2B levels in the cortex. Anodal tDCS increases the infarct size, exacerbates cortical hemorrhages and disruptions of the blood brain barrier, increases the number of caspase-3+ cells in the cortex and striatum, and increases lactate levels in the cortex. |
| Pedron et al., 2014 | Swiss mice | F | 4 mo | Nicotine abstinence in addicted mice | Unilateral frontal cortex | 57.14 | 5 x 2 | Anodal tDCS has antidepressant properties, improves working memory, and reduces conditioned place preference for nicotine in normal animals. In nicotine-addicted mice, it reduces locomotor activity, depression-related behavior, and addictive behaviors. |
Abbreviations: 6-OHDA, 6-hydroxydopamine; A1R, Adenosine A1 receptor; CA3, cornu ammonis 3; CFA, complete Freund’s adjuvant; CSD, cortical spreading depression; fMRI, functional magnetic resonance imaging; LTD, long-term depression; GAP-43, growth associated protein-43; Iba1, ionized calcium-binding adapter molecule; MAP-2, microtubule-associated protein-2; MCAO, middle cerebral artery occlusion, mRNA, messenger ribonucleic acid; NR2B, N-methyl D-aspartate receptor aubtype 2B; NS, not specified; tDCS, transcranial direct current stimulation; TNF-α = tumor necrosis factor α.