MBDB, a derivative of amphetamine that releases little or no dopamine, caused rats to become hyperactive and suppressed their exploratory behaviors, similar to the effects of MDMA. This hyperactivity lasted over 60 minutes at higher doses. Pretreatment with fluoxetine, a serotonin reuptake inhibitor, blocked MBDB-induced hyperactivity, indicating that the behavioral effects depend on serotonin release rather than dopamine release. Fluoxetine also blocked hyperactivity from related drugs S-(+)3,4-methylenedioxyamphetamine and p-chloroamphetamine. Tissue measurements showed decreased serotonin and its metabolite 5-HIAA after MBDB or S-(+)MDMA, which was prevented by fluoxetine. S-(+)MDMA increased dopamine levels in a fluoxetine-sensitive manner, suggesting serotonin release may indirectly influence dopamine.
Injecting S-MDMA (a form of MDMA, or ecstasy) directly into a brain region called the nucleus accumbens made rats more active, similar to the effect of amphetamine. Blocking serotonin with fluoxetine did not prevent this hyperactivity, even though it blocks the effects of systemically given S-MDMA. A drug that only releases serotonin, MBDB, did not increase activity when injected into the nucleus accumbens, though it does when given systemically. These results suggest that S-MDMA's effects in the nucleus accumbens are due to its ability to release catecholamines like dopamine, not serotonin, and differ from its systemic actions.