Rapid Effect of Nicotine Intake on Neuroplasticity in Non-Smoking Humans

Abstract

In various studies nicotine has shown to alter cognitive functions in non-smoking subjects. The physiological basis for these effects might be nicotine-generated modulation of cortical structure, excitability, and activity, as mainly described in animal experiments. In accordance, a recently conducted study demonstrated that application of nicotine for hours via nicotine patch in non-smoking humans alters the effects of neuroplasticity-inducing non-invasive brain stimulation techniques on cortical excitability. Specifically, nicotine abolished inhibitory plasticity independent from the focality of the stimulation protocol. While nicotine prevented also the establishment of non-focal facilitatory plasticity, focal synapse-specific facilitatory plasticity was enhanced. These results agree with a focusing effect of prolonged nicotine application on facilitatory plasticity. However, since nicotine induces rapid adaption processes of its receptors, this scenario might differ from the effect of nicotine in cigarette smoking. Thus in this study we aimed to gain further insight in the mechanism of nicotine on plasticity by exploring the effect of nicotine spray on non-focal and focal plasticity-inducing protocols in non-smoking subjects, a fast-acting agent better comparable to cigarette smoking. Focal, synapse-specific plasticity was induced by paired associative stimulation (PAS), while non-focal plasticity was elicited by transcranial direct current stimulation (tDCS). Forty eight non-smokers received nicotine spray respectively placebo combined with one of the following protocols (anodal tDCS, cathodal tDCS, PAS-25, and PAS-10). Corticospinal excitability was monitored via motor-evoked potentials elicited by transcranial magnetic stimulation (TMS). Nicotine spray abolished facilitatory plasticity irrespective of focality and PAS-10-induced excitability diminution, while tDCS-derived excitability reduction was delayed and weakened. Nicotine spray had thus a clear effect on neuroplasticity in non-smoking subjects. However, the effects of nicotine spray differ clearly from those of prolonged nicotine application, which might be due to missing adaptive nicotinic receptor alterations. These results enhance our knowledge about the dynamic impact of nicotine on plasticity, which might be related to its heterogenous effect on cognition.

Smoking Restores Impaired LTD-Like Plasticity in Schizophrenia: a Transcranial Direct Current Stimulation Study

“…In the intervention groups receiving either prolonged nicotine patch application (Thirugnanasambandam et al, 2011) or fast-acting nicotine nasal spray application (Grundey et al, 2012a), the results of these studies showed a reduced or abolished LTD-like neuroplasticity response following cathodal tDCS. With regard to our findings in healthy smokers, one comparable study showed a significant MEP reduction Smoking restores LTD-like plasticity in schizophrenia W Strube et al following cathodal tDCS in healthy subjects under nicotine withdrawal for 10 h, but only a trendwise MEP reduction following nicotine patch application (Grundey et al, 2012b). As in our experimental setup, only a short period of nicotine withdrawal preceded the experiments and these subjects displayed related LTD-like plasticity responses, as did healthy subjects following prolonged nicotine patch application (Grundey et al, 2012b), so one might argue that our withdrawal duration may be insufficient to restore nicotine-related abolishment of plasticity.…”

“…With regard to our findings in healthy smokers, one comparable study showed a significant MEP reduction Smoking restores LTD-like plasticity in schizophrenia W Strube et al following cathodal tDCS in healthy subjects under nicotine withdrawal for 10 h, but only a trendwise MEP reduction following nicotine patch application (Grundey et al, 2012b). As in our experimental setup, only a short period of nicotine withdrawal preceded the experiments and these subjects displayed related LTD-like plasticity responses, as did healthy subjects following prolonged nicotine patch application (Grundey et al, 2012b), so one might argue that our withdrawal duration may be insufficient to restore nicotine-related abolishment of plasticity. The effects in smokers might therefore be at least partially determined by an impact of nicotine.…”

“…Studies applying cathodal tDCS in healthy nonsmokers for plasticity induction showed either a reduction or even an abolishment of LTD-like plasticity following prolonged and fast-acting nicotine application (Grundey et al, 2012a;Thirugnanasambandam et al, 2011). Further investigations on chronic smokers during nicotine withdrawal revealed unaffected LTD-like plasticity following cathodal tDCS, which was abolished following nicotine reapplication (Grundey et al, 2012b). Moreover, physiological investigations with transcranial magnetic stimulation (TMS) indicate that chronic smoking tilts the balance between facilitation and inhibition towards cortical hypoexcitability (Grundey et al, 2013;Lang et al, 2008).…”

“…Given the well-established inhibitory deficit in schizophrenia in various brain regions, including the primary motor cortex (Hashimoto et al, 2008b), the positive impact of nicotine in pronouncing inhibitory functions , and the concept of smoking-related self-medication, we hypothesized that smoking schizophrenia patients would display fewer deficits in LTD-like plasticity compared with nonsmoking patients. On the basis of previous publications (Grundey et al, 2012b), we further hypothesized that healthy smokers and nonsmokers would display differences in LTD-like plasticity following cathodal tDCS. We also hypothesized that smoking and nonsmoking healthy subjects would show different plasticity responses compared with the respective schizophrenia patients.…”

Brain effects of Nicotine and derived compounds

“…In fact, the investigation by several research groups about the effect of nicotine on attention (Kadir et al, 2006) and learning and memory have given heterogeneous results (Smith et al, 2006). Grundey et al (2012) show new evidence of a negative effect of nicotine spray on facilitatory plasticity and a diminished reduction in excitability after transcranial direct current stimulation. These results differ from the effects observed after chronic nicotine administration.…”