Potential explanation for the differential effects of genetic 5-HTT downregulation in humans and rodents on fear conditioning, expression, extinction, and extinction recall. 5-HT may strengthen associative learning processes, and thereby the association between a CS and shock (CS-shock memory trace). During extinction subjects acquire a second memory, namely, between the CS and safety (CS-safety memory trace). It depends on the competition between the two, what the behavioural expression of subjects will be. Because 5-HTT−/− knockout rodents and 5-HTTLPR s-allele carriers are sensitive to motivationally relevant stimuli, the CS-shock memory trace may be “stronger” than the CS-safety memory trace, and thus prevail. The specific environmental conditions (e.g., housing, novelty) may determine at which phase (conditioning, expression, extinction, extinction recall) this CS-shock memory is expressed.
