Prior MDMA exposure inhibits learning and produces both tolerance and sensitization in the radial-arm maze

Recent research using the partially-baited radial arm maze with rats has shown that acute or single-session high-dose exposure to +/-3,4-methylenedioxymethaphemtamine (MDMA) impairs reference memory processes more so than working memory processes. The current study examined the effect that an initial binge exposure of MDMA had on the ability to learn this task and whether such exposure produced tolerance or sensitization to subsequent low dose acute MDMA exposure. Following either an initial binge dose (4×10mg/kg) of MDMA or saline, rats received regular weekly injections of either MDMA (4.0mg/kg) or saline during task acquisition training. Although eventually able to acquire the task at a level comparable to controls, initial binge MDMA exposure significantly impaired task acquisition. Binge-treated rats displayed evidence of a tolerance effect to subsequent acute injections of MDMA; although with continued training this tolerance effect was reduced. However, initial binge treatment also produced a sensitized response to subsequent acute MDMA exposure that manifested as a prolonged period of impairment up to 24h following administration. Consistent with the effects seen following other regimes of exposure to MDMA, the pattern of errors made was best described as an impairment to reference memory processes as opposed to working memory processes.