Interactions between 3,4-methylenedioxymethamphetamine and σ1 receptors

Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) are structurally similar and represent a serious and growing health threat. Earlier studies in our laboratory have shown that methamphetamine interacts with σ receptors and that antagonism of these receptors can attenuate methamphetamine-induced locomotor stimulation and neurotoxicity. However, no research exists which characterizes the interaction between σ receptors and MDMA. Therefore, the goal of the present study was to determine whether σ receptors are involved in the actions of MDMA. In the first part of the study, competition and saturation binding assays were performed to measure the interaction of MDMA with σ receptors. The receptor binding assays revealed that MDMA interacts preferentially with the σ1 subtype, as compared to the σ2 subtype, and that this interaction occurs in a competitive manner. The second part of the study focused on behavioral measurements in male, Swiss Webster mice to determine whether a selective σ1 receptor antagonist, BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine, 0-30 mg/kg, i.p.) could attenuate the locomotor stimulant actions of MDMA (0-50 mg/kg, i.p.). BD1063 alone had no effect on locomotor activity, but dose-dependently attenuated the locomotor stimulant effects of MDMA and produced a significant shift to the right in the MDMA dose response curve. Together, the data support the functional relevance of the interaction of MDMA with σ1 receptors, and suggest that these receptors are involved in the stimulant actions of MDMA.