Nicotine modulates human brain plasticity via calcium‐dependent mechanisms

Abstract

Nicotine (NIC) modulates neuroplasticity and improves cognitive performance in animals and humans mainly by increased calcium permeability and modulation of diverse transmitter systems. NIC administration impairs calcium-dependent plasticity induced by non-invasive brain stimulation with transcranial direct current stimulation (tDCS) in non-smoking participants probably as a result of intracellular calcium overflow. To test this hypothesis, we analysed the effect of calcium channel blockade with flunarizine (FLU) on anodal tDCS-induced cortical excitability changes in healthy non-smokers under NIC. We applied anodal tDCS combined with NIC patch and FLU at three different doses (2.5, 5 and 10 mg) or with placebo medication. NIC abolished anodal tDCS-induced neuroplasticity. Under medium dosage (but not under low and high dosage) of FLU combined with NIC, plasticity was re-established. For FLU alone, the lowest dosage weakened long-term potentiation (LTP)-like plasticity, whereas the highest dosage again abolished tDCS-induced plasticity. The medium dosage turned LTP-like plasticity in long-term depression-like plasticity. The results of the present study suggest a key role of calcium influx and calcium levels in nicotinic effects on LTP-like plasticity in humans. This knowledge might be relevant for the development of new therapeutic strategies in cognitive dysfunction.

Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons

“…Previous attempts into this direction have used microdosing in volunteers with deuterium-labeled compounds (Harada et al 2016 ). Concerning the question of neurological consequences, controlled short-term experiments with volunteers have been performed to study effects of nicotine (Grundey et al 2018 ). Whether such studies would be ethically acceptable for pesticides is doubtful for most countries in Europe.…”

Expanding the parameter space of anodal transcranial direct current stimulation of the primary motor cortex

“…Specifically, for anodal tDCS, increasing the current intensity from 1 to 2 mA did not result in a corresponding increase of MEP amplitudes 26,29 . Changes in cortical excitability due to tDCS are calcium-dependent 14,31 , and for LTP induction, calcium concentration within a specific range is required 21 . It could thus be argued that for the previous studies with relatively low tDCS intensities and/or short durations, these were at the lower limit of respective calcium concentrations.…”

Consequences of prefrontal tDCS on inhibitory control and reactive aggression

“…There is emerging evidence that tDCS may have differential effects on complex behaviors based on a multitude of influences such as genetics ( Plewnia et al , 2013 ; Nieratschker et al , 2015 ), nicotine intake ( Grundey et al , 2018 ) and individual characteristics ( Shen et al , 2016 ) and might thus depend on the study population. For instance, while decreasing risk-taking in healthy participants, the same tDCS protocol leads to increased risk-taking in marijuana users ( Pascual-Leone et al , 2007 ; Boggio et al , 2010 ).…”

“…We investigate male patients diagnosed with alcohol dependence and healthy matched controls. Given the high prevalence of tobacco smoking in addictive disorders such as alcohol dependence ( Guydish et al , 2016 ) and the indication that nicotine may affect the effects of tDCS ( Grundey et al , 2018 ), we also include an additional group that consisted of male chronic tobacco users (TU). Using a double-blind, sham-controlled study design, performance in a modified Taylor Aggression Paradigm (mTAP) and the SSRT, two widely used and well-validated tasks, is assessed before and immediately after a single session of tDCS.…”