Other amphetamine-like compounds may involve mechanisms mediated by other monoamine systems. Thus, work with methylenedioxymethamphetamine (MDMA) has focused on SERT. The locomotor stimulant effects of MDMA are abolished in SERT KO mice (Bengel, et al., 1998), as is MDMA-induced serotonin release and MDMA self-administration (Trigo, et al., 2007). Surprisingly, and perhaps indicating non-SERT mediated mechanisms in some of the effects of MDMA, increases in extracellular dopamine levels in the nucleus accumbens in SERT KO mice after administration of MDMA are unchanged (Trigo, et al., 2007) or reduced (Hagino, et al., 2011). In the latter study, the effects of MDMA on dopamine release were only eliminated in combined DAT/SERT KO mice. Other evidence supports a role of dopamine in the effects of MDMA, as well as more generally supporting one of the major themes that has emerged from many of these KO studies, that there are substantial interactions between dopamine and serotonin systems in the rewarding effects of psychostimulants. For example, male dopamine receptor D1 KO mice show significant increases in MDMA-induced hyperactivity compared to WT mice, while DRD2 KO mice exhibit reductions in MDMA-induced hyperactivity (Risbrough, et al., 2006).
