Nicotinergic impact on focal and non-focal neuroplasticity induced by non-invasive brain stimulation in non-smoking humans

Neuropsychopharmacology. 2011 Mar;36(4):879-86. doi: 10.1038/npp.2010.227. Epub 2010 Dec 15.


Nicotine improves cognitive performance and modulates neuroplasticity in brain networks. The neurophysiological mechanisms underlying nicotine-induced behavioral changes have been sparsely studied, especially in humans. Global cholinergic activation focuses on plasticity in humans. However, the specific contribution of nicotinic receptors to these effects is unclear. Henceforth, we explored the impact of nicotine on non-focal neuroplasticity induced by transcranial direct current stimulation (tDCS) and focal, synapse-specific plasticity induced by paired associative stimulation (PAS) in healthy non-smoking individuals. Forty-eight subjects participated in the study. Each subject received placebo and nicotine patches combined with one of the stimulation protocols to the primary motor cortex in different sessions. Transcranial magnetic stimulation (TMS)-elicited motor-evoked potential (MEP) amplitudes were recorded as a measure of corticospinal excitability until the evening of the second day following the stimulation. Nicotine abolished or reduced both PAS- and tDCS-induced inhibitory neuroplasticity. Non-focal facilitatory plasticity was also abolished, whereas focal facilitatory plasticity was slightly prolonged by nicotine. Thus, nicotinergic influence on facilitatory, but not inhibitory plasticity mimics that of global cholinergic enhancement. Therefore, activating nicotinic receptors has clearly discernable effects from global cholinergic activation. These nicotine-generated plasticity alterations might be important for the effects of the drug on cognitive function.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Electric Stimulation / methods
  • Female
  • Humans
  • Male
  • Motor Cortex / drug effects*
  • Motor Cortex / physiology*
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Nicotine / pharmacology*
  • Smoking*
  • Transcranial Magnetic Stimulation / methods*
  • Young Adult


  • Nicotine