Differential modulations of response control processes by 5-HT1A gene variation

Response selection and control are supposed to reflect important basal ganglia functions. Recently, we showed that the dopaminergic system may be especially important for response selection in compatible, but not in incompatible stimulus-response (S-R) relations. Research indicates that the dopaminergic system is influenced by the serotonergic system, but little is known about the involvement of the serotonergic system in response selection. Analyzing event-related potentials (ERPs) in a sample of healthy probands (N=74), we show the 5-HT1A C(-1019)G polymorphism modulating response-related processes, as reflected in the N2 component, in compatible, but not incompatible, S-R relations. This modulation was a function of the number of -1019 G alleles. Decreasing numbers of -1019 G alleles were stepwise related to increases in the N2 on compatible trials and concomitant increases in response times. The functional effect of the 5-HT1A C(-1019)G polymorphism has previously been shown to be specific for serotonergic 1 A autoreceptors of serotonergic neurons in the dorsal raphe nucleus (DRN). Due to this close relation of genotype effects to neuroanatomically dissociable structures, the results suggest that DRN serotonin 1 A autoreceptors are important for compatible S-R relations, i.e., response selection, but not for incompatible S-R relations, i.e. response conflict or inhibition. The results extend previous findings on the dopaminergic system to the serotonergic system. The examined functions are precisely regulated on a neuronal level, since neurophysiological and behavioural effects are driven in an allele-dose fashion. Because of this, the results are of importance for future clinical applications.