The amphetamine analog 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), has become increasingly popular as a “recreational” drug, particularly among young people. Cognitive impairment has been associated with frequent use of MDMA in humans and learning deficits have been observed after chronic MDMA treatment in different animal models. These deficits might be related to the neurotoxic effect of MDMA on 5HT nerve terminals. It has also been shown in animal behavioral models that acute administration of MDMA can affect learning and memory. Nevertheless, there is no information regarding the effects of MDMA upon synaptic plasticity models as Long Term Potentiation (LTP) and Long Term Depression (LTD), which are involved in learning and memory processes. We studied the effect of acute application of MDMA on the induction of LTP and LTD in visual cortical brain slices and hippocampus. Slices 400 μm thick were obtained from 3-5 week-old Sprague-Dawley rats, killed by decapitation under halothane anesthesia according with the guidelines of the Ethics Committee of the University of Santiago, and maintained in artificial cerebrospinal fluid for 1 hr before recording. Field EPSPs were evoked with electrical stimulation using bipolar electrodes. For visual cortex, LTP or LTD were recorded in layer 2/3 after either tetanic or low frequency stimulation protocols applied to layer 4, respectively. For hippocampal slices, LTP or LTD was recorded in CA1 by stimulation applied from Schaeffer collaterals, using similar protocols. MDMA was superfused during 20 min (10 min before and after the electrical stimulation). Statistical significance for mean differences between experimental and control groups were assessed using Mann-Whitney U test. In the visual cortex LTP and LTD were inhibited of dose-dependent manner by MDMA. LTP was inhibited from +50± 3% (S.E.M., n=8) in control experiments to +20±3% (S.E.M., n=7) in sliced superfused with 50 μM MDMA (Z=2.37, P<0.05). LTD inhibition was from -35±10 % (S.E.M., n=5) in controls to -15±5%(S.E.M., n=5) in treated (Z=-2.0, P<0.05). Inhibition induced by MDMA was reverted removing the drug from the bath and after to apply a second tetanus. Interestedly and contrarily to expected, in hippocampus MDMA induced a doses-dependent increase in the induction of LTP. LTP in presence of 50 μM MDMA was of +170±25%(S.E.M., n=8), where slice in control situation was of +50±3%(S.E.M., n=8; Z=-2.58, P<0.001). Non-significant effect was observed in LTD (Z=-0.85, P=0.39). These results show for the first time a direct effect of MDMA on the induction of LTP and LTD, which might be associated with the learning and memory deficits observed in human and animal models.