Dosage-Dependent Effect of Dopamine D2 Receptor Activation on Motor Cortex Plasticity in Humans

Abstract

The neuromodulator dopamine plays an important role in synaptic plasticity. The effects depend on receptor subtypes, affinity, concentration level, and the kind of neuroplasticity induced. In animal experiments, dopamine D 2 -like receptor stimulation revealed partially antagonistic effects on plasticity, which might be explained by dosage dependency. In humans, D 2 receptor block abolishes plasticity, and the D 2 /D 3 , but predominantly D 3 , receptor agonist ropinirol has a dosage-dependent nonlinear affect on plasticity. Here we aimed to determine the specific affect of D 2 receptor activation on neuroplasticity in humans, because physiological effects of D 2 and D 3 receptors might differ. Therefore, we combined application of the selective D 2 receptor agonist bromocriptine (2.5, 10, and 20 mg or placebo medication) with anodal and cathodal transcranial direct current stimulation (tDCS), which induces nonfocal plasticity, and with paired associative stimulation (PAS) generating a more focal kind of plasticity in the motor cortex of healthy humans. Plasticity was monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. For facilitatory tDCS, bromocriptine prevented plasticity induction independent from drug dosage. However, its application resulted in an inverted U-shaped dose-response curve on inhibitory tDCS, excitability-diminishing PAS, and to a minor degree on excitability-enhancing PAS. These data support the assumption that modulation of D 2 -like receptor activity exerts a nonlinear dose-dependent effect on neuroplasticity in the human motor cortex that differs from predominantly D 3 receptor activation and that the kind of plasticity-induction procedure is relevant for its specific impact.

Effect of tDCS on auditory hallucinations in schizophrenia: Influence of catechol-O-methyltransferase (COMT) Val158Met polymorphism

“…Contextually, Met carriers in our study demonstrating significantly lesser percentage reduction of auditory hallucinations is in tune with these previous observations (Plewnia et al, 2013). Dopaminergic basis has been postulated to underlie the plasticity modulation effects of tDCS (Fresnoza et al, 2014). Thus, the observed finding might be linked to the differential effects of COMT Val158Met polymorphism on cortical dopamine levels.…”

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016

“…While neurophysiological studies in healthy individuals have established a short-term interaction between tDCS and pharmacological agents [71], [72], [8], [73], there is minimal information on the interaction between tDCS and pharmacologic intervention in the treatment of mood disorders. The available evidence suggest potential synergistic effects at least in the treatment of depression [74],[75],[69].…”

Repeated application of Modafinil and Levodopa reveals a drug-independent precise timing of spatial working memory modulation

“…inverted-U-shaped dose-response profiles of postsynaptic dopamine effects in the prefrontal cortex has been described for working memory [11,14,29,30]. Similar dosedependent effects of D2 receptors on neuronal plasticity have been described in human motor cortex [31,32] while D2 was antagonized for L-Dopa stimulation of D1 [33]. Skinbjerg et al [34] reported a decrease in in vivo radio-ligand binding to the dopamine 2 receptor during PET studies after amphetamine induced increased extracellular dopamine for several hours.…”