Abstract
Most therapeutic candidates for treating attention-deficit hyperactivity disorder (ADHD) have focused on modulating the dopaminergic neurotransmission system with neurotrophic factors. Regulation of this system by transcranial direct current stimulation (tDCS) could contribute to the recovery of cognitive symptoms observed in patients with ADHD. Here, male spontaneously hypertensive rats (SHR) were subjected to consecutive high-definition tDCS (HD-tDCS) (20 min, 50 μA, current density 63.7 A/m2, charge density 76.4 kC/m2) over the prefrontal cortex. This treatment alleviated cognitive deficits, with an increase in tyrosine hydroxylase and vesicular monoamine transporter two and significantly decreased plasma membrane reuptake transporter (DAT). HD-tDCS application increased the expression of several neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF), and activated hippocampal neurogenesis. Our results suggest that anodal HD-tDCS over the prefrontal cortex may ameliorate cognitive dysfunction via regulation of DAT and BDNF in the mesocorticolimbic dopaminergic pathways, and therefore represents a potential adjuvant therapy for ADHD.
Highlights
Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous neuropsychiatric disorder highly prevalent in children, characterized by impairments in attention and/or hyperactivity-impulsivity (Faraone et al, 2015; Tsai, 2017)
In the open-field test, the spontaneously hypertensive (SHR) and sham animals showed significant hyperactivity compared to the Wistar-Kyoto rat (WKY) group, which was reduced by HD-transcranial direct current stimulation (tDCS) and MPH treatment, especially in the tDCS-PFC group (Figure 1A, F(5,42)=5.984, p
In the Y-maze, the tDCS-M1 group showed a significant decrease in time spent in the new arm compared to the spontaneously hypertensive rats (SHR) group in the modified version; the tDCS-PFC and MPH groups showed significantly increased spontaneous alternation compared to the sham group in the alternation task, especially with respect to same-arm returns (SAR) (Figure 1C and D, F(5,36)=0.750, p=0.591 and Figure 1—figure supplement 1C and D)
Summary
Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous neuropsychiatric disorder highly prevalent in children, characterized by impairments in attention and/or hyperactivity-impulsivity (Faraone et al, 2015; Tsai, 2017) Psychostimulants, such as amphetamine and methylphenidate (MPH) that work by increasing central dopamine and norepinephrine activity in the brain, are recommended as first-line pharmacological therapy for patients with ADHD (Faraone, 2018). The pathogenesis of ADHD is not fully understood, but genetic factors play a significant role in its development (Kent, 2004). Most therapeutic candidates have focused on modulating the dopaminergic neurotransmission system, with additional candidates involving the noradrenergic and serotonergic systems (Banaschewski et al, 2010; Kent, 2004).
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