Behavioral Profiles in Rats Distinguish Among "Ecstasy," Methamphetamine and 2,5-Dimethoxy-4-Iodoamphetamine: Mixed Effects for "Ecstasy" Analogues

Abstract

3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”) is a psychoactive drug structurally related to other phenylisopropylamines acting as stimulants or hallucinogens in humans. Although MDMA has a pharmacological identity of its own, the distinction of its acute effects from those of stimulants or even hallucinogens is controversial. In this work, dose-response curves (0.25, 0.5, 1, 3, 5, and 10 mg/kg) representing the acute in vivo effects of MDMA were compared with those of a structurally related stimulant (methamphetamine, MA) and a hallucinogenic analogue (2,5-dimethoxy-4-iodoamphetamine, DOI) in a set of behavioral protocols in rats, including spontaneous psychomotor activity, anxiolytic/ anxiogenic-like effects and active avoidance conditioning responses. The behavioral profiles obtained allowed us to differentiate among racemic MDMA, MA, and DOI at different dose ranges. In addition, the evaluation of four MDMA analogues (1, 5, and 10 mg/kg) comprising two well-known MDMA analogues (MDA [3,4-methylenedioxyamphetamine] and MDE (N-ethyl-MDA, believed to substitute for MDMA) and two other structural analogues (MDOH [N-hydroxy-MDA] and MMDA-2 [2-methoxy- 4,5-methylenedioxyamphetamine]) showed that none of these exactly resembles MDMA in their pharmacological profiles, highlighting the unique character of this prototypical entactogen. In fact, their effects exhibited similarities with the behavioral profiles of either MA or DOI, as well as novel profiles in specific behavioral paradigms.