Mechanisms of Nicotinic Modulation of Glutamatergic Neuroplasticity in Humans.
The impact of nicotine (NIC) on plasticity is thought to be primarily determined via calcium channel properties of nicotinic receptor subtypes, and glutamatergic plasticity is likewise calcium-dependent. Therefore glutamatergic plasticity is likely modulated by the impact of nicotinic receptor-dependent neuronal calcium influx. We tested this hypothesis for transcranial direct current stimulation (tDCS)-induced long-term potentiation-like plasticity, which is abolished by NIC in nonsmokers. To reduce calcium influx under NIC, we blocked N-methyl-d-aspartate (NMDA) receptors. We applied anodal tDCS combined with 15 mg NIC patches and the NMDA-receptor antagonist dextromethorphan (DMO) in 3 different doses (50, 100, and 150 mg) or placebo medication. Corticospinal excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor-evoked potential amplitudes after plasticity induction. NIC abolished anodal tDCS-induced motor cortex excitability enhancement, which was restituted under medium dosage of DMO. Low-dosage DMO did not affect the impact of NIC on tDCS-induced plasticity and high-dosage DMO abolished plasticity. For DMO alone, the low dosage had no effect, but medium and high dosages abolished tDCS-induced plasticity. These results enhance our knowledge about the proposed calcium-dependent impact of NIC on plasticity in humans and might be relevant for the development of novel nicotinic treatments for cognitive dysfunction.
Laboratory of Cognitive Sciences and Neuropsychopharmacology, Program of Post-Graduation in Physiological Sciences, Federal University of Espírito Santo, Vitória-ES, Brazil.|Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Göttingen 37075, Germany.
Marcelo Di Marcello Valladão
MDMV
Lugon
Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Göttingen 37075, Germany.
Giorgi
G
Batsikadze
Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Göttingen 37075, Germany.
Shane
S
Fresnoza
Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Göttingen 37075, Germany.
Jessica
J
Grundey
Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Göttingen 37075, Germany.
Min-Fang
MF
Kuo
Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Göttingen 37075, Germany.
Walter
W
Paulus
Laboratory of Cognitive Sciences and Neuropsychopharmacology, Program of Post-Graduation in Physiological Sciences, Federal University of Espírito Santo, Vitória-ES, Brazil.
Ester Miyuki
EM
Nakamura-Palacios
Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Göttingen 37075, Germany.|Leibniz Research Centre for Working Environment and Human Resources, Dortmund, Germany.|Department of Neurology, University Medical Hospital Bergmannsheil, Bochum, Germany.
Michael A
MA
Nitsche
D000328:Adult; D000704:Analysis of Variance; D003915:Dextromethorphan / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D065908:Transcranial Direct Current Stimulation
D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D009538:Nicotine; D003915:Dextromethorphan
dextromethorphan; neuroplasticity; nicotine; nicotinic receptors; transcranial direct current stimulation