Compromised neuroplasticity in cigarette smokers under nicotine withdrawal is restituted by the nicotinic α 4 β 2-receptor partial agonist varenicline

Sci Rep. 2017 May 3;7(1):1387. doi: 10.1038/s41598-017-01428-6.


Nicotine modulates neuroplasticity and improves cognitive functions in animals and humans. In the brain of smoking individuals, calcium-dependent plasticity induced by non-invasive brain stimulation methods such as transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS) is impaired by nicotine withdrawal, but partially re-established after nicotine re-administration. In order to investigate the underlying mechanism further, we tested the impact of the α4β2-nicotinic receptor partial agonist varenicline on focal and non-focal plasticity in smokers during nicotine withdrawal, induced by PAS and tDCS, respectively. We administered low (0.3 mg) and high (1.0 mg) single doses of varenicline or placebo medication before stimulation over the left motor cortex of 20 healthy smokers under nicotine withdrawal. Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor evoked potential amplitudes for 36 hours after plasticity induction. Stimulation-induced plasticity was absent under placebo medication, whereas it was present in all conditions under high dose. Low dose restituted only tDCS-induced non-focal plasticity, producing no significant impact on focal plasticity. High dose varenicline also prolonged inhibitory plasticity. These results are comparable to the impact of nicotine on withdrawal-related impaired plasticity in smokers and suggest that α4β2 nicotinic receptors are relevantly involved in plasticity deficits and restitution in smokers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cigarette Smoking / adverse effects
  • Cigarette Smoking / physiopathology*
  • Electric Stimulation
  • Evoked Potentials, Motor / drug effects
  • Female
  • Humans
  • Male
  • Motor Cortex / drug effects
  • Motor Cortex / physiopathology
  • Neuronal Plasticity / drug effects*
  • Nicotine / adverse effects*
  • Nicotinic Agonists / administration & dosage*
  • Receptors, Nicotinic / physiology*
  • Substance Withdrawal Syndrome / physiopathology*
  • Transcranial Direct Current Stimulation
  • Varenicline / administration & dosage*
  • Young Adult


  • Nicotinic Agonists
  • Receptors, Nicotinic
  • nicotinic receptor alpha4beta2
  • Nicotine
  • Varenicline