The purpose of the present study was to examine how genetic variability in the promoter of the SLC6A4 gene encoding the serotonin transporter (5-HTT) may influence induction of long-term potentiation (LTP). The genotyping of the 53 healthy volunteers was performed by a combination of TaqMan assay and gel electrophoresis. Based on the transcription rates, the subjects were divided in 3 groups; 5-HTT SS, 5-HTT SL(G)/L(A)L(G)/SL(A) and 5-HTT L(A)L(A). The intensity of pain to test stimuli was rated on a visual analog scale (VAS). High frequency stimulation (HFS) conditioning applied to one arm was used to induce LTP. Only a minor change in pain was observed following the HFS conditioning evoked by electrical test stimuli delivered through the conditioning electrode. Moreover, the change in pain evoked by test stimuli delivered through the conditioning electrode was not related to the 5-HTT genotype. However, we observed a clear increase in pain following the HFS conditioning evoked by mechanical pin-prick test stimuli delivered at the skin adjacent to the conditioning. Also, the 9 individuals with the 5-HTT SS genotype reported more pain than individuals with 5-HTT SL(G)/L(A)L(G)/SL(A) genotype following HFS conditioning on mechanical pin-prick test stimuli. Thus, the present data show that induction of the perceptual correlate of human LTP is associated with the genetic variability in the gene encoding the 5-HTT. Taken together, this suggests that the expression of 5-HTT, may be important for induction of LTP in humans.
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