title: Effect of the Nicotinic α4β2-receptor Partial Agonist Varenicline on Non-invasive Brain Stimulation-Induced Neuroplasticity in the Human Motor Cortex.
abstract: Nicotine alters cognitive functions in animals and humans most likely by modification of brain plasticity. In the human brain, it alters plasticity induced by transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS), probably by interference with calcium-dependent modulation of the glutamatergic system. We aimed to test this hypothesis further by exploring the impact of the α4β2-nicotinic receptor partial agonist varenicline on focal and non-focal plasticity, induced by PAS and tDCS, respectively. We administered low (0.1 mg), medium (0.3 mg), and high (1.0 mg) single doses of varenicline or placebo medication before PAS or tDCS on the left motor cortex of 25 healthy non-smokers. Corticospinal excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor evoked potential amplitudes up to 36 h after plasticity induction. Whereas low-dose varenicline had no impact on stimulation-induced neuroplasticity, medium-dose abolished tDCS-induced facilitatory after-effects, favoring focal excitatory plasticity. High-dose application preserved cathodal tDCS-induced excitability diminution and focal excitatory PAS-induced facilitatory plasticity. These results are comparable to the impact of nicotine receptor activation and might help to further explain the involvement of specific receptor subtypes in the nicotinic impact on neuroplasticity and cognitive functions in healthy subjects and patients with neuropsychiatric diseases.
authors.affiliation: Department of Clinical Neurophysiology, Georg-August-University of Göttingen, Göttingen 37075, Germany.
authors.forename: Giorgi
authors.initials: G
authors.lastname: Batsikadze
authors.affiliation: Department of Clinical Neurophysiology, Georg-August-University of Göttingen, Göttingen 37075, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Paulus
authors.affiliation: Department of Clinical Neurophysiology, Georg-August-University of Göttingen, Göttingen 37075, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Grundey
authors.affiliation: Department of Clinical Neurophysiology, Georg-August-University of Göttingen, Göttingen 37075, Germany.
authors.forename: Min-Fang
authors.initials: MF
authors.lastname: Kuo
authors.affiliation: Department of Clinical Neurophysiology, Georg-August-University of Göttingen, Göttingen 37075, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nitsche
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001703:Biophysics; D004305:Dose-Response Relationship, Drug; D019054:Evoked Potentials, Motor / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000187:drug effects* / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D065908:Transcranial Direct Current Stimulation; D050781:Transcranial Magnetic Stimulation; D000068580:Varenicline / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D018722:Nicotinic Agonists; D000068580:Varenicline
keywords: human motor cortex; neuroplasticity; nicotine; paired associative stimulation; transcranial direct current stimulation