Effects of nicotine on PAS-induced neuroplasticity in the healthy human

Introduction: Nicotine enhances cognitive performance in humans probably based on nicotinergic effects on neuroplasticity. So far these effects could just be shown in animal experiments. Aim of our study is therefore to explore the nicotinergic modulation of PAS-induced neuroplasticity in healthy humans. Results from animal studies have shown, that nicotine is a strong inductor and modulator of cortical activity and neuroplasticity (Gu 2002). Hereby it has an impact on processes of learning and memory, not only in animals but also human beings (Poorthuis et al. 2009). The intention of our study is to explore the impact of nicotine on PAS-induced synapse-specific neuroplasticity in nonsmokers.

Material: Altogether 12 healthy non-smokers participated in our study (6 male, 6 female). Plasticity was induced by the paired associative stimulation (PAS), which has been shown to induce long-lasting excitability changes by combining operipheral nerve stimulation and single-pulse TMS-stimulation. As model served the motor cortex. Depending on the intervall between peripheral and cortical stimulation, this protocoll leads to long-lasting inhibition (PAS10, 10ms intervall) or fascilitation (PAS25; 25ms). PAS-induced plasticity was explored before and after administration of nicotine patch (16mg). Cortical excitability changes were monitored via TMS-induced MEP of the motor cortex until the next morning.

Results: Exposition to nicotine prolonged the PAS-induced excitability enhancement from 90 up to 120 minutes after PAS. Furthermore, administration of nicotine patch lead to a complete extinction of PAS-induced excitability diminution compared to the non-nicotine condition.

Conclusion: Non-smokers display a reduced inhibitory and an enhanced and prolonged facilitatory plasticity after administration of nicotine patch. A possible explanation might be an altered intracellular calcium concentration induced by activitation of nicotinergic acetylcholine-receptors. Since learning process and long-term potentiation are closely related phenomenon, the modulation of neuroplasticity by nAchR could be based on the effect of nicotine on cognitive performance.

Literature: Poorthuis RB, Goriounova NA, Couey JJ, Mansvelder HD. Nicotinic actions on neuronal networks for cognition: general principles and long-term consequences. Biochem Pharmacol. 2009 Oct 1;78(7):668–76.

Gu Q. Neuromodulatory transmitter systems in the cortex and their role in cortical plasticity. Neuroscience. 2002;111:815–35.