Nonlinear Dose-Dependent Impact of D1 Receptor Activation on Motor Cortex Plasticity in Humans

Abstract

The neuromodulator dopamine plays an important role in synaptic plasticity. The effects are determined by receptor subtype specificity, concentration level, and the kind of neuroplasticity induced. D1-like receptors have been proposed to be involved in cognitive processes via their impact on plasticity. Cognitive studies in humans and animals revealed a dosage-dependent effect of D1-like receptor activation on task performance. In humans, D1-like receptor activation re-establishes plasticity under D2 receptor block. However, a dosagedependent effect has not been explored so far. To determine the impact of the amount of D1-like receptor activation on neuroplasticity in humans, we combined sulpiride, a selective D2 receptor antagonist, with the dopamine precursor L-DOPA (25, 100, and 200 mg) or applied placebo medication. The impact on plasticity induced by anodal and cathodal transcranial direct current stimulation (tDCS) was compared with the impact on plasticity induced by excitatory and inhibitory paired associative stimulation (PAS) at the primary motor cortex of healthy humans. Stimulation-generated cortical excitability alterations were monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. D1-like receptor activation produced an inverted U-shaped dose-response curve on plasticity induced by both facilitatory tDCS and PAS. For excitability-diminishing tDCS and PAS, aftereffects were abolished or converted trendwise into facilitation. These data extend findings of dose-dependent inverted U-shaped effects of D1 receptor activation on neuroplasticity of the motor cortex.

Chronic Enhancement of Serotonin Facilitates Excitatory Transcranial Direct Current Stimulation-Induced Neuroplasticity

“…This might be explained by the activation of different 5-HT receptor subtypes, the concentration of 5-HT agonists and antagonists, and different brain sites of action (Mori et al, 2001;Staubli and Otaky, 1994). To explore the reasons for these inconsistent results and to learn more about the impact of serotonin on neuroplasticity in humans, future studies should consider specific serotonergic receptor subtypes, apply different 5-HT-receptor agonists and antagonists, and explore the impact of different dosages, which might be a relevant factor for the strength and direction of effects, as seen for other neuromodulators, which have nonlinear effects on plasticity (Frensnoza et al, 2014;Monte-Silva et al, 2010).…”

TMS and drugs revisited 2014

“…Low (25 mg) and high (200 mg) doses of L-Dopa abolished anodal tDCS-induced LTP-like plasticity (Monte-Silva et al, 2010), and even turned PASinduced LTP-like plasticity into LTD-like plasticity (Thirugnanasambandam et al, 2011b). These effects were largely reproduced by selective stimulation of D1Rs (Fresnoza et al, 2014) or D2Rs (Monte-Silva et al, 2009). In contrast, a medium (Thirugnanasambandam et al, 2011b).…”

“…In contrast, a medium (Thirugnanasambandam et al, 2011b). These effects of a medium L-Dopa dose may depend on the balance of D1R-and D2R-stimulation as selective stimulation of either receptor produces different effects (Fresnoza et al, 2014;Monte-Silva et al, 2009). In addition, data suggested that the modulatory effects of dopamine depend on the NIBS protocol applied.…”

Double dissociation of working memory and attentional processes in smokers and non-smokers with and without nicotine

“…Cohens' d and effect size r for paired t tests effects of nicotine cannot be ruled out and were not explicitly surveyed so far but are known for neuromodulators like dopamine(Fresnoza et al 2014;Monte-Silva et al 2011).…”