The effects of MDMA (5 and 10 mg/kg) on locomotion and dopamine (DA) release in the nucleus accumbens were examined in Fischer 344 and Lewis rats. Lewis rats are believed to be more prone to addiction-like behaviors than Fischer rats. Locomotor activity was measured via photobeam movement detector and DA in nucleus accumbens was measured in freely moving animals via microdialysis. DA was detected via HPLC in 11 samples collected every 20 min for a period of 220 min. MDMA only produced hyperactivity in Fischer rats, and only at 10 mg/kg. However, despite this difference in locomotor response, rat strains did not differ with respect to levels of DA in nucleus accumbens, with plateau levels appearing 100 to 120 minutes after drug administration in Fischer and Lewis rats. The authors reject pharmacokinetic explanations for increased locomotion in Fischer rats after MDMA on the grounds that previous research found greater methamphetamine levels in Lewis rats than in Fischer rats, and they reject explanations based on the concept of there being "functional" versus "non-functional" fractions of dopamine release. The authors conclude that rat strain differences in MDMA-induced hyperactivity relate to other brain areas, not the nucleus accumbens. It is unclear whether findings from this cross-strain comparison shed light on possible human differences in response to MDMA, but does indicate that in rats, increased locomotor activity after MDMA is either not directly associated with dopamine release or is jointly controlled by dopaminergic and non-dopaminergic brain areas. It should be noted that a detailed study of MDMA hyperactivity reported findings suggesting a role for 5HT2C receptors (Fletcher et al. 2002).