Transcranial direct current stimulation improves short-term memory in an animal model of attention-deficit/hyperactivity disorder

Douglas Teixeira Leffa; Andressa de Souza; Vanessa Leal Scarabelot; Liciane Fernandes Medeiros; Carla de Oliveira; Eugenio Horacio Grevet; Wolnei Caumo; Diogo Onofre de Souza; Luis Augusto Paim Rohde; Iraci L S Torres

doi:10.1016/j.euroneuro.2015.11.012

Transcranial direct current stimulation improves short-term memory in an animal model of attention-deficit/hyperactivity disorder

Eur Neuropsychopharmacol. 2016 Feb;26(2):368-377. doi: 10.1016/j.euroneuro.2015.11.012. Epub 2015 Dec 1.

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, RS 90035-003, Brazil; Biochemistry Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, 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 Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, 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.
³ 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, RS 90035-003, 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 Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; ADHD Outpatient Program, Hospital de Clínicas de Porto Alegre, Brazil.
⁵ Post-Graduate Program in Medicine: Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
⁶ Biochemistry Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
⁷ Department of Psychiatry, 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, RS 90035-003, 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: iracitorres@gmail.com.

PMID: 26792443
DOI: 10.1016/j.euroneuro.2015.11.012

Abstract

Attention deficit hyperactivity disorder (ADHD) is characterized by impairing levels of hyperactivity, impulsivity and inattention. However, different meta-analyses have reported disruptions in short and long-term memory in ADHD patients. Previous studies indicate that mnemonic dysfunctions might be the result of deficits in attentional circuits, probably due to ineffective dopaminergic modulation of hippocampal synaptic plasticity. In this study we aimed to evaluate the potential therapeutic effects of a neuromodulatory technique, transcranial direct current stimulation (tDCS), in short-term memory (STM) deficits presented by the spontaneous hypertensive rats (SHR), the most widely used animal model of ADHD. Adult male SHR and Wistar Kyoto rats (WKY) were subjected to a constant electrical current of 0.5 mA intensity applied on the frontal cortex for 20 min/day during 8 days. STM was evaluated with an object recognition test conducted in an open field. Exploration time and locomotion were recorded, and brain regions were dissected to determine dopamine and BDNF levels. SHR spent less time exploring the new object when compared to WKY, and tDCS improved object recognition deficits in SHR without affecting WKY performance. Locomotor activity was higher in SHR and it was not affected by tDCS. After stimulation, dopamine levels were increased in the hippocampus and striatum of both strains, while BDNF levels were increased only in the striatum of WKY. These findings suggest that tDCS on the frontal cortex might be able to improve STM deficits present in SHR, which is potentially related to dopaminergic neurotransmission in the hippocampus and striatum of those animals.

Keywords: ADHD; Dopamine; Memory; SHR; tDCS.

Publication types

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

MeSH terms

Analysis of Variance
Animals
Attention Deficit Disorder with Hyperactivity / complications*
Attention Deficit Disorder with Hyperactivity / pathology
Brain / metabolism
Brain-Derived Neurotrophic Factor / metabolism
Disease Models, Animal
Dopamine / metabolism
Locomotion / physiology
Male
Memory Disorders / etiology*
Memory Disorders / therapy*
Memory, Short-Term / physiology*
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Recognition, Psychology / physiology
Statistics as Topic
Transcranial Direct Current Stimulation*

Substances

Brain-Derived Neurotrophic Factor
Dopamine