Researchers investigated the anti-Parkinson’s disease (PD) effects of MDMA (2.5, 5 and 10 mg/kg) and related compounds using model in rats. Dopamine neurons in the left medial forebrain bundle were lesioned with 6-hydroxydopamine (6OHDA), with norepinephrine neurons protected by desipramine coadministration. Post-lesion, the researchers gave rats the dopamine agonist apomorphine (0.25 mg/kg), MDMA (2.5, 5 and 10 mg/kg), MDE, MDA and MBDB (all 5 mg/kg). Apomorphine was administered an unspecified number of days post-lesion (at least 1 day later), and subsequent substances were administered after a 5-day washout period; all rats received each test drug. Apomorphine produced contralateral, or rightward, turning (in the direction opposite the lesion), an apparent model of dystonia associated with Parkinson’s disease medications. Turning in the direction of the lesion (ipsilateral rotation) was treated as a sign of treating dystonia. In order to assess contributions made by serotonin release on MDMA’s effects on movement after lesioning, the researchers also injected MDMA after citalopram pretreatment (10 mg/kg). Researchers also tested MDMA’s ability to trigger leftward rotation after serotonin depletion by first giving rats p-chlorophenylalanine (PCPA), a serotonin synthesis inhibitor for 3 consecutive days before receiving MDMA. Rats given apomorphine walked in rightward circles, in the direction opposite the lesion, and saline-treated rats had a slight tendency toward leftward rotation. Rats circled in a leftward direction after injections of 5 and 10 mg/kg MDMA, but not after injections of 2.5 mg/kg MDMA. Rats exhibited the most rotational behavior (walking in circles) 70-90 minutes post-MDMA, and 80 minutes post-MDA. 5 mg/kg MDE and 5 mg/kg MBDB did not significantly increase leftward rotation, whereas MDA and MDMA (5 mg/kg) both did so, with MDA producing the greatest increase. Rats that received citalopram pretreatment prior to 5 mg/kg MDMA demonstrated significantly reduced leftward rotation after MDMA. Leftward rotation after 5 mg/kg MDMA was only slightly reduced after 3 days of PCPA, a sign that reduced serotonin did not interfere with this effect. The authors note that ipsilateral rotation is also seen after lesioned rats received amphetamine, suggesting that release of striatal dopamine may play a role in producing ipsilateral rotation. This hypothesis is supported by the fact that the dopamine-releasing capability in the entactogens tested in this study parallels their potency at causing leftward rotation. Because citalopram pretreatment reduced MDMA-induced ipsilateral rotation, the serotonin system may also be involved in producing ipsilateral rotation in lesioned rats. The researchers propose other possible modes of action for MDMA and related drugs, including striatal dopamine release resulting from activity at 5HT₂ receptors, norepinephrine release, action at adrenergic (norepinephrine) receptors, or a currently unknown action of MDMA and related drugs. This paper was published simultaneously along with another paper assessing anti-cataleptic effects of MDMA (Banjaw et al. 2003), with both papers published subsequent to an initial investigation of anti-Parkinsonian effects of MDMA (Schmidt et al. 2002). Finding MDA to be most effective in producing leftward rotation stands in contrast to its proving ineffective at reducing haloperidol-induced catalepsy (Schmidt et al. 2002). This is surprising, and suggests that the two models of Parkinson’s disease symptoms used in these studies may assess different pharmacological or brain activities.