(From Science Vol 373 Issue 6560, September 10, 2021)
Li et al. found that cocaine SA in mice that express a SERT that blocks cocaine binding (SertKI mice) (8) does not increase extracellular serotonin concentrations, but unexpectedly, this causes increased transition to compulsion compared with that in wild-type (WT) mice. The population of perseverers of SertKI mice in cocaine SA is comparable with that of WT mice in the oDASS group. The authors also found that although oDASS-mediated addiction results in compulsion in more than half of individuals, systemic administration of citalopram, which is a serotonin-selective reuptake inhibitor, during acquisition of addiction through oDASS reduces compulsion transition to the same amount in cocaine SA of WT mice (∼20% perseverers). These results indicate that increased extracellular serotonin prevents the transition to compulsion.