The intriguing effects of ecstasy (MDMA) on cognitive function in mice subjected to a minimal traumatic brain injury (mTBI)

Rationale: The use of ecstasy (MDMA) among young adults has dramatically increased over the years. Since MDMA may impair the users' driving ability, the risk of being involved in a motor vehicle accident (MVA) is notably increased. Minimal traumatic brain injury (mTBI) a common consequence of MVAs-produces short- and long-term physical, cognitive, and emotional impairments. Objectives: To investigate the effects of an acute dose of MDMA in mice subjected to closed head mTBI. Methods: Mice received 10 mg/kg MDMA 1 h prior to the induction of mTBI. Behavioral tests were conducted 7 and 30 days post-injury. In addition to the behavioral tests, phosphorylation of IGF-1R, ERK, and levels of tyrosine hydroxylase (TH) were measured. Results: mTBI mice showed major cognitive impairments in all cognitive tests conducted. No additional impairments were seen if mTBI was preceded by one dose of MDMA. On the contrary, a beneficial effect was seen in these mice. The western blot analysis of TH revealed a significant decrease in the mTBI mice. These decreases were reversed in mice that were subjected to MDMA prior to the trauma. Conclusions: The presence of MDMA at the time of mTBI minimizes the alteration of visual and spatial memory of the injured mice. The IGF-1R pathway was activated due to mTBI and MDMA but was not the main contributor to the cognitive improvements. MDMA administration inverted the TH decreases seen after injury. We believe this may be the major cause of the cognitive improvements seen in these mice.