Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters

Douglas Teixeira Leffa; Bruna Bellaver; Artur Alban Salvi; Carla de Oliveira; Wolnei Caumo; Eugenio Horacio Grevet; Felipe Fregni; André Quincozes-Santos; Luis Augusto Rohde; Iraci L S Torres

doi:10.1016/j.brs.2018.04.001

Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters

Brain Stimul. 2018 Jul-Aug;11(4):743-751. doi: 10.1016/j.brs.2018.04.001. Epub 2018 Apr 5.

Affiliations

¹ Post-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.
² Biochemistry Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
³ 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.
⁴ Post-Graduate Program in Medicine: Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Pain and Palliative Care Service, Laboratory of Pain & Neuromodulation, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
⁵ Psychiatry Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; ADHD Outpatient Program, Hospital de Clínicas de Porto Alegre, Brazil.
⁶ Laboratory of Neuromodulation, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard University, Boston, United States.
⁷ Psychiatry Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; ADHD Outpatient Program, Hospital de Clínicas de Porto Alegre, Brazil; National Institute of Developmental Psychiatry for Children and Adolescents, Brazil.
⁸ Post-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. Electronic address: iltorres@hcpa.edu.br.

PMID: 29656905
DOI: 10.1016/j.brs.2018.04.001

Abstract

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.

Keywords: ADHD; SHR; tDCS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Attention Deficit Disorder with Hyperactivity / therapy*
Brain / metabolism
Brain / physiopathology
Cytokines / metabolism*
Male
Memory, Long-Term*
Oxidative Stress*
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Transcranial Direct Current Stimulation / methods*

Substances

Cytokines