The acute and sub-chronic effects of MDMA on anxiety in mice was assessed by examining time spent in elevated arms of elevated plus maze and number of open versus closed arm entries in mice given vehicle, 1, 8, or 15 mg/kg MDMA acutely or daily on five consecutive days. 8 mg/kg MDMA acutely increased anxiety (reduced time in open arms, increased time in central area) when compared with controls. 1 mg/kg showed significant increase in some anxiety-related plus-maze behaviors, but not all, and there were no significant differences from controls at 15 mg/kg). Sub-chronic administration of both 1 and 8 mg/kg MDMA increased anxiety, as indicated by decreased time spent in open arms and more time spend in closed (walled) arms. 15 mg/kg produced reduced time in closed arms, a marker of reduced anxiety. The authors interpret results as demonstrating acute anxiogenic effects of one dose of MDMA only, and mostly anxiogenic effects of sub-chronic doses of MDMA. Since the researchers did not perform histological studies of brain serotonin and dopamine, the observed sub-chronic increase in anxiety cannot be treated as an indicator of MDMA neurotoxicity. There are a number of other studies examining the effects of acute and chronic exposure to MDMA on anxiety in rodents, with conflicting findings of both increased and decreased anxiety (e.g. Fone et al. 2002; Mechan et al. 2002; Morley et al. 2002, and see Green 2002 for a brief review). However, recent studies in humans have been unable to find a clear link between regular ecstasy use and psychological problems (e.g. Daumann et al. 2001; Morgan et al. 2002; Lieb et al. 2002), and it is unclear how findings in rodents relate to effects in humans.