Fig. 4

A Schematic Representation of MDMA’s Sites of Action in Frontal Cortex. This figure summarizes the effects of a single-dose (15 mg/kg, intraperitoneal) 3,4-methylenedioxymethamphetamine (MDMA) administration 3 weeks earlier on the frontal cortex (FC) of Dark Agouti rats and provides a hypothetical framework. On one hand, neurons of neuronal networks within this region seem to suffer wide-scale downregulations (marked with numbers in blue circles in the neuron on the right hand side) in their basic functions, like transport processes, chromatin maintenance and protein synthesis and localization, as a possible consequence of MDMA’s free radical producing and hyperthermic effects. Since the downregulated processes would be important mechanisms for neuronal survival, neuronal networks might suffer from the loss of basic functions of individual cells. As compensation on a network basis, upregulations of the long-term potentiation (LTP) genes (like Camk2g calcium/calmodulin dependent kinase subunit and NMDA-receptor subunit Grin2b, marked by numbers in red circles in the neuron on the left hand side) along with pathway level upregulations suggest a possible ongoing recovery (as shown in bottom right). Please, note, changes represent mRNA level up/downregulations, no protein levels were measured