Mechanisms of Nicotinic Modulation of Glutamatergic Neuroplasticity in Humans

What does this mean for our needed neuroplasticity? Should we be taking nicotine? Via smoking? Patches? Gum? eCigarettes? Whom the hell is going to answer that simple question? Our fucking failures of stroke associations can once again prove their fucking failures by not even knowing that answering this question could help survivors recover.
http://cercor.oxfordjournals.org/content/early/2015/10/21/cercor.bhv252.abstract

1. Marcelo Di Marcello Valladão Lugon1,2,
2. Giorgi Batsikadze2,
3. Shane Fresnoza2,
4. Jessica Grundey2,
5. Min-Fang Kuo2,
6. Walter Paulus2,
7. Ester Miyuki Nakamura-Palacios1,† and
8. Michael A. Nitsche2,3,4,†

+ Author Affiliations

1. ¹Laboratory of Cognitive Sciences and Neuropsychopharmacology, Program of Post-Graduation in Physiological Sciences, Federal University of Espírito Santo, Vitória-ES, Brazil
2. ²Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Göttingen 37075, Germany
3. ³Leibniz Research Centre for Working Environment and Human Resources, Dortmund, Germany
4. ⁴Department of Neurology, University Medical Hospital Bergmannsheil, Bochum, Germany

1. Address correspondence to Dr Michael A. Nitsche, Leibniz Research Centre for Working Environment and Human Resources, Ardeystr. 67, 44139 Dortmund, Germany. Email: nitsche@ifado.de

1. ↵† Ester Miyuki Nakamura-Palacios and Michael A. Nitsche contributed equally to this study.

Abstract

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.