Oh, celexa also blocks there damage from mdma. And here is the science behind it. Remember, no MAOI, even hours after. High doses of MDMA have a two-phase effect on serotonergic functioning, first causing acute decreases, then partial recovery, then chronic decreases. For example, after a single dose of 10 mg/kg MDMA to a rat, release of 5-HT leads to depletion of tissue levels of 5-HT and its metabolite 5-HIAA within 3 hours of dosing (Schmidt 1987; Stone, 1987b). Approximately 6 hours later, levels begin to return to normal, but this recovery is not sustained. About 24 hours after dosing, 5-HT levels begin a second, sustained decrease and remain significantly lower than baseline 2 weeks later. This sustained decrease is thought to be associated with axonal damage.
The intracellular enzyme TPH follows a similar time course, with decreased activity occurring within 15 minutes of drug administration. However, there is less short-term recovery of TPH activity in comparison to 5-HT. The recovery of TPH activity appears to involve regeneration of enzyme that was inactivated by oxidation rather than synthesis of new enzyme. SERT functioning is also altered. When rats were given 15 mg/kg subcutaneous MDMA and sacrificed an hour later, the uptake of serotonin was decreased by 80% (Fleckenstein, 1999). It should be noted that significant acute 5-HT depletions are not necessarily produced by all active doses of MDMA. Schmidt (1986) reported that 2.5 mg/kg MDMA did not produce an acute decrease in 5-HT or 5HIAA in Sprague Dawley rats at 3 hours after injection. Of note, Kish (2000) did find striatal 5-HT depletions in a chronic ecstasy user who died shortly after ecstasy ingestion. This suggests that at least some of the doses administered by humans are sufficient to produce 5-HT depletions.
The above description focuses on serotonergic changes because these are used too measure toxicity. Many other acute neurochemical changes occur after MDMA exposure. For example, dopamine is released (Stone, 1986) and dopamine transporter reuptake activity is decreased within 1 hr of high dose MDMA (Fleckenstein, 1999; Metzger, 1998). MDMA can also acutely increase dopamine synthesis (Nash, 1990). As noted previously, mice are selectively vulnerable to MDMA-induced dopaminergic neurotoxicity (Logan, 1988; Miller,1994; Stone, 1987a). In some studies, long-term alterations in dopaminergic functioning have been seen in other species (e.g., rats in Commins, 1987).
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.
Slow recovery of serotonergic functioning can be seen following a neurotoxic dose of MDMA. The extent of recovery is different in different species. In rats, there is extensive recovery of indicators of serotonergic functioning 1 year after drug exposure (Battaglia, 1988; Lew, 1996; Sabol, 1996; Scanzello, 1993), although there is significant variation in recovery between individual animals (Fischer, 1995). In primates, some recovery of serotonergic function occurs but is less extensive than in the rat. Altered serotonergic axon density was still detectable 7 years after MDMA exposure in one study of squirrel monkeys (Hatzidimitriou, 1999). Therefore, despite some recovery, MDMA-induced serotonergic changes are likely permanent in this primate species. This apparent species difference may be partially related to the more severe initial serotonergic damage usually seen in primates compared to rats, but also likely indicates a species difference in regrowth of serotonergic axons.
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