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Transcranial direct current stimulation improves long-term memory deficits in an animal model of
Douglas Teixeira Leffa1, Bruna Bellaver2, Artur Alban Salvi3
1Post-Graduate Program in Medicine: Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Laboratory of Pain Pharmacology and Neuromodulation: Pre Clinical Studies - Pharmacology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Background:
Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear.
Objective/Hypothesis:
We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS.
Methods:
Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated.
Results:
TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines.
Conclusion:
TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored.
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