MDMA Self-Administration in Laboratory Animals: A Summary of the Literature and Proposal for Future Research

Abstract

The prevalence of 3,4-methylenedioxymethamphetamine (MDMA) use has increased globally and the pattern of consumption has changed considerably. Previously, a subculture of MDMA users was fairly restricted to the dance club scene. More recently, use has spread outside of this subculture and now many users consume MDMA frequently and in large amounts and some meet criteria for drug abuse and/or dependence. Because of confounds associated with studying drug users and abusers, animal models have been employed to investigate potential consequences of drug-taking. Among these, self-administration by laboratory animals has been shown to have excellent predictive validity. There have, however, been mixed results with respect to the ability of MDMA to support and maintain self-administration by laboratory animals. This paper reviews the literature on MDMA self-administration in laboratory primates and rodents. Most of the studies in laboratory animals suggest that only low levels of MDMA are self-administered on a daily basis but some have indicated high levels of self-administered MDMA in certain subjects. Differences might be dependent upon the number of test sessions, prior training conditions or other paradigmatic variables. In most cases, MDMA was found to be a lower efficacy reinforcer than other drugs of abuse. It is suggested that the MDMA self-administration develops following a decrease in MDMA-produced serotonin release that occurs with repeated exposure over an extended period of testing. It is hypothesized that the deficit in central serotonin increases the relative MDMA-produced dopamine responses and that this increase in the dopamine response underlies the development and maintenance of MDMA self-administration.

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

“…Of particular significance for abuse potential testing is whether effects of mixed-action DA/ NE/5HT releasers like MDMA or the cathinone derivative mephedrone (Bonano et al, 2014) might change during repeated/chronic treatment. For example, selfadministration studies with MDMA suggest that repeated exposure during acquisition of self-administration can produce tolerance to 5HT effects and increased expression of DA-mediated reinforcing effects (Schenk, 2009). Preliminary data from our laboratory suggest that a similar phenomenon occurs during repeated mephedrone treatment, such that repeated treatment produces decreased expression of 5HT-mediated rate-decreasing effects and increased expression of DA-mediated rateincreasing effects (J. Bonano and S.S. Negus, unpublished observations).…”

Modelos animales de adicción a las drogas

“…Ventajas e inconvenientes de la AA. La popularidad de su uso radica en que este modelo cuenta con una excelente validez predictiva, ya que existe una gran similitud entre los resultados obtenidos con dicho modelo en animales y las conductas adictivas humanas (Koob et al, 2014;Mead, 2014;Schenk, 2009;Soria, Barbano, Maldonado y Valverde, 2008). Es decir, comparado con otros modelos de adicción, el paradigma de AA está muy relacionado con el abuso en humanos en cuanto a la forma de administración de la sustancia y a la respuesta conductual que se genera para conseguir la administración de la misma (O'Connor, Chapman, Butler y Mead, 2011).…”

“…Otro inconveniente del modelo de AA es que para la utilización correcta de dicha técnica es necesario entrenar a los animales para que aprendan a adquirir la conducta operante. Dicho inconveniente es más acusado con drogas cuyo poder reforzante inicial no es excesivamente elevado, como puede ser la 3,4-metilendioximetanfetamina (MDMA o éxtasis) (Trigo, Panayi, Soria, Maldonado y Robledo, 2006;Schenk, 2009), por lo que en estos casos el animal es previamente entrenado con una sustancia más reforzante como la cocaína (Schenk, 2009) o se administra una dosis priming previa (Trigo et al, 2006). Incluso en algunos casos, se utiliza un patrón de restricción alimentaria antes de la fase de adquisición de la AA (Soria et al, 2005).…”

Mice in Ecstasy: Advanced Animal Models in the Study of MDMA

“…MDMA has been shown to have reinforcing properties in humans [108,109]. Murine, rat and monkey experimental models have also shown the rewarding properties of MDMA [109][110][111][112][113][114][115][116].…”

“…Murine, rat and monkey experimental models have also shown the rewarding properties of MDMA [109][110][111][112][113][114][115][116]. These models typically make use of conditioned place preference (CPP) tests (which evaluate the preference of an animal for a chamber in which it previously received MDMA) and operant intravenous self-administration tests.…”