Importance of ERK activation in behavioral and biochemical effects induced by MDMA in mice
British Journal of Pharmacology – October 29, 2003
Source: OpenAlex
Summary
MDMA, at a dose of 9 mg/kg, significantly enhanced conditioned place preference (CPP) in CD-1 mice, indicating its rewarding effects. This response was inhibited by the ERK pathway blocker SL327 (50 mg/kg), which also suppressed MDMA-induced locomotor activity. Real-time PCR revealed that MDMA triggered c-fos transcription in key brain areas, including the caudate putamen and nucleus accumbens. Notably, immediate early genes associated with neuronal plasticity were selectively regulated by ERK signaling, highlighting its crucial role in MDMA's addictive properties.
Abstract
Little is known about the cellular effects induced by 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy), although changes in gene expression have been observed following treatments with other psychostimulants. Thus, the aim of this study was to investigate in mice, the relationships between the ras‐dependent protein kinase ERK and MDMA‐induced reinforcement using the conditioned place preference (CPP) and locomotor activity measurements. This was completed using real‐time quantitative PCR method by a study of immediate early‐genes (IEGs) transcription known to be involved in neuronal plasticity. A significant CPP was observed after repeated MDMA treatment in CD‐1 mice at a dose of 9 mg kg −1 i.p. but not at 3 and 6 mg kg −1 . This rewarding effect was abolished by the selective inhibitor of ERK activation, SL327 (50 mg kg −1 ; i.p.). Similar results were obtained on MDMA‐induced locomotor activity, clearly suggesting a role of ERK pathway in these behavioral responses. Following acute i.p. injection, MDMA induced a strong c‐fos transcription in brain structures, such as caudate putamen, nucleus accumbens and hippocampus, whereas egr‐1 and egr‐3 transcripts were only increased in the caudate putamen. MDMA‐induced IEGs transcription was selectively suppressed by SL327 in the caudate putamen, suggesting a role for other signaling pathways in regulation of IEGs transcription in the other brain structures. In agreement with these results, MDMA‐induced c‐fos protein expression was blocked by SL327 in the caudate putamen. This study confirms and extends to mice the reported role of ERK pathway in the development of addiction‐like properties of MDMA. This could facilitate studies about the molecular mechanism of this process by using mutant mice. British Journal of Pharmacology (2003) 140 , 831–838. doi: 10.1038/sj.bjp.0705506