Therapeutic effects of anodal transcranial direct current stimulation in a rat model of ADHD

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 (SHR) rats 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 2 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.

Predicting Individual Treatment Response to rTMS for Motor Recovery After Stroke: A Review and the CanStim Perspective

“…This association between BDNF genotype and rTMS response has however not been confirmed in a separate study utilizing inhibitory contralesional rTMS ( 41 ). Some evidence from pre-clinical studies in rats seems to suggest that non-invasive brain stimulation may directly increase the expression of BDNF , facilitate neurogenesis ( 71 ) and enhance BDNF affinity for tyrosine receptor kinase B (TrkB), a neurotrophin receptor ( 72 ). This would result in a direct modulation of synaptic plasticity mediated by BDNF -TrkB-NDMA receptors ( 73 ).…”

Preclinical Evidence for the Mechanisms of Transcranial Direct Current Stimulation in the Treatment of Psychiatric Disorders; A Systematic Review

“…Anodal stimulation enhances glutamatergic transmissions, 9 which leads to insertion of AMPA receptors, usually stored in endosome vesicles, into the postsynaptic membrane. 10 Moreover, Ca 2+ flows facilitated by glutamatergic transmissions 9 activate signal cascades, and phosphorylate CREB, 11,12 which promotes protein synthesis 9,[11][12][13][14][15] and establishes the late LTP. 9,[15][16][17] LTPs are considered to improve functional connectivity between brain regions [18][19][20] and efficiency of information processing 12,13,16,20,21 (see Table 3).…”

“…The CREB then activates transcription of the target gene to synthesize new proteins, 11,12 eg, AMPA receptors, 9 NMDA receptors, 16,17 ion channels and intracellular signal proteins, 12,13,15 which enhances synaptic binding. 11,12 The establishment of the late LTP has been shown to be accompanied with the induction of brain-derived neurotrophic factor (BDNF), 12,13,15 glial cell line derived neurotrophic factor (GDNF), 15 nerve growth factor (NGF), 15 as well as increased expressions of growth-related proteins, such as growth-associated protein-5 (GAP-5) 14 and GAP-43. 9 Recent investigations also report tDCS produces hippocampal neurogenesis in rat models of ADHD 15 or cerebral infarction.…”

“…20 16 and phosphorylates CREB through activation of CaMKII. The CREB then activates transcription of the target gene to synthesize new proteins, eg, AMPA receptors, 9 NMDA receptors, 16,17 which are mediated by BDNF, 12,13,15 GDNF, NGF, 15 Arc, and c-Fos. 11,12 Abbreviations: FC, frontal cortex; HIP, hippocampus; MC, motor cortex; STR, striatum; ACC, anterior cingulate cortex; CaMKII, Ca 2 + /calmodulin-dependent protein kinase II; CREB, cAMP response element-binding protein; BDNF, brain-derived neurotrophic factor; GDNF, glial cell line derived neurotrophic factor; NGF, nerve growth factor; Arc, activity-regulated cytoskeleton-associated protein; GAP, growth-associated protein; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA, N-methyl-D-aspartate.…”

Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4

“…We recognize the limitations of the study due to the use of male subjects only. This is not unique to this impulsivity study (Bellés et al, 2021;Jung et al, 2020;Zapata and Lupica, 2021). We chose to study males not only because surveys by the World Health Organization show a significant gender bias towards males in the prevalence of ADHD (Fayyad et al, 2017) but also to allow us to compare our findings to those of previous studies cited in this paper (Isherwood et al, 2017).…”