The role of the SLC6A3 3’ UTR VNTR in nicotine effects on cognitive, affective, and motor function

Abstract

Rationale Nicotine has been widely studied for its pro-dopaminergic effects. However, at the behavioural level, past investigations have yielded heterogeneous results concerning effects on cognitive, affective, and motor outcomes, possibly linked to individual differences at the level of genetics. A candidate polymorphism is the 40-base-pair variable number of tandem repeats polymorphism (rs28363170) in the SLC6A3 gene coding for the dopamine transporter (DAT). The polymorphism has been associated with striatal DAT availability (9R-carriers > 10R-homozygotes), and 9R-carriers have been shown to react more strongly to dopamine agonistic pharmacological challenges than 10R-homozygotes. Objectives In this preregistered study, we hypothesized that 9R-carriers would be more responsive to nicotine due to genotype-related differences in DAT availability and resulting dopamine activity. Methods N=194 non-smokers were grouped according to their genotype (9R-carriers, 10R-homozygotes) and received either 2-mg nicotine or placebo gum in a between-subject design. Spontaneous blink rate (SBR) was obtained as an indirect measure of striatal dopamine activity and smooth pursuit, stop signal, simple choice and affective processing tasks were carried out in randomized order. Results Reaction times were decreased under nicotine compared to placebo in the simple choice and stop signal tasks, but nicotine and genotype had no effects on any of the other task outcomes. Conditional process analyses testing the mediating effect of SBR on performance and how this is affected by genotype yielded no significant results. Conclusions Overall, we could not confirm our main hypothesis. Individual differences in nicotine response could not be explained by rs28363170 genotype.

Neural mechanisms of background and velocity effects in smooth pursuit eye movements

“…Contrary to our hypotheses, we did not observe interactions of background and target velocity for any of the dependent variables although we had purposely selected stimuli conditions that had yielded a strong interactive effect in a prior behavioural study (Schröder et al, 2021). A reason for this discrepancy could be that pursuit performance was generally worse compared to previous laboratory investigations using similar tasks (Meyhöfer et al, 2019;Schröder et al, 2021;Schröder et al, 2022) presumably because of the unusual and uncomfortable environment in the scanner and distracting external stimuli such as scanner noise in this study (see also Koch et al, 2003). Therefore, it can be assumed that participants did not reach optimal performance levels and thus more subtle effects such as the interaction reported previously could not emerge.…”

The Experiences of Patients with Schizophrenia on Smoking and Cessation: A Qualitative Study

“…In a study examining the effects of smoking on mood, it was stated that smoking had a calming effect on anger in women and on anger and sadness in men (23) and that nicotine replacement has been shown to be effective in controlling agitation in smokers with schizophrenia (9). In the literature, it has been defined that smoking and environmental factor such as stress are associated, and the assumption that patients with schizophrenia tend to selfmedicate by smoking due to symptoms of mental illness, drug side effects and cognitive deficits has been mentioned (24). Also, the relationship between recurrent disease course and stressful life events in schizophrenia has been investigated, and it has been reported that patients with schizophrenia tend to experience stress more intensely and that this is caused by less effective approaches to coping with stress (25).…”