About half of rats fail to acquire MDMA self-administration, and the difference is not due to how the drug is metabolized. MDMA triggers greater release of serotonin than dopamine in the brain. Rats that did acquire self-administration showed lower serotonin overflow than those that did not. Destroying serotonin neurons with a toxin made more rats acquire MDMA self-administration and speeded acquisition of cocaine self-administration. These findings suggest that serotonin limits initial sensitivity to MDMA's rewarding effects and delays reliable self-administration.
Impulsivity, but not novelty-seeking, predicts how strongly rats seek MDMA after withdrawal. Before self-administration, rats were tested for impulsivity (premature responding on a five-choice task) and novelty-seeking (locomotor activity in a novel environment). Impulsivity was positively correlated with the magnitude of drug-seeking triggered by MDMA, while novelty-seeking showed no significant link to either acquisition or drug-seeking. MDMA self-administration also caused transient deficits in attention and increased premature responses. The findings suggest impulsivity may be a risk factor for compulsive drug-seeking after MDMA withdrawal.
About half of a large sample of rats learned to self-administer MDMA, taking an average of 16 daily sessions before meeting the initial criterion. When the dose was reduced, the rats increased their responding in a compensatory manner. Over an additional 14 days of self-administration, daily intake rose from 8.5 to 15.25 mg/kg. These results indicate that MDMA acts as a reliable reinforcer for roughly half of rats, and that acquiring self-administration requires more sessions than is typical for other abused drugs.