The time course of damaging events in rats can be seen by administering SSRIs, such as fluoxetine and citalopram, after MDMA. Pretreatment with fluoxetine (Prozac) or citalopram (Celexa) has been shown to block the neurotoxicity of MDMA (Battaglia, 1988; Schmidt 1987; 1990; Shankaran, 1999a), probably by blocking interactions of MDMA with SERT. More interestingly, fluoxetine remains almost fully protective if given 3 or 4 hours after MDMA. By 4 hours, most of the MDMA-induced release of 5-HT and DA has already occurred (Gough, 1991; Hiramatsu, 1990) and increases in extracellular free radicals (Colado, 1997b; Shankaran, 1999a) and lipid peroxidation (the alteration of fat molecules by free radicals) (Colado, 1997a) can be measured. Nevertheless, the administration of fluoxetine at this point decreases subsequent extracellular oxidative stress (Shankaran, 1999a) and long-term 5-HT depletions (Schmidt, 1987; Shankaran, 1999a). Fluoxetine will still be partially protective if given 6 hours after MDMA but has no protective effect 12 hours after administration (Schmidt, 1987). This shows that neurotoxic MDMA regimens initiate a series of events that become increasingly damaging between 3 and 12 hours after drug administration in rats.
