The effects of co-administration of 3,4-methylenedioxymethamphetamine (“ecstasy”) or para-methoxyamphetamine and moclobemide at elevated ambient temperatures on striatal 5-HT, body temperature and behavior in rats

Mechanisms and environmental factors that underlying the intensification of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-induced serotonin syndrome in rats

“…7B), consistent with previous studies (O'Shea et al, 2005). There are other reports demonstrating that 5HT concentrations was increased while environmental temperatures as a single factor were used for the studies (Stanley et al, 2007; Feduccia et al, 2011). The inconsistency may be attributed to numerous differences between experimental designs, particularly drug dosages used in other studies.…”

“…Recently, the difference between animal and human data has been reconciled by animal tests carried out under distinct environments to mimic such rave scenarios (Turner and Parrott, 2000; Parrott, 2012b). Several environmental factors have been investigated, including warm ambient temperatures, physical activity, loud music, lights and crowded situations (Malberg and Seiden, 1998; Fantegrossi et al, 2003; Iannone et al, 2006; Stanley et al, 2007; Von Huben et al, 2007; Gilpin et al, 2011). Despite many efforts, the environment explored in laboratory tests appears to have very moderate effects on MDMA toxicity (Green et al, 2004b; Shortall et al, 2013) unless a huge dose, (e.g., 20-40 mg/kg) was used for animals (Gordon et al, 1991; Malberg and Seiden, 1998).…”

Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats

“…Although Benamar et al (2008) have recently used microdialysis to report that hypothalamic dopamine release may correlate with hyperthermia produced by systemic administration of very high doses of MDMA, they failed to demonstrate that the temperature rise could be prevented by administration of dopamine antagonists in the microdialysate, which would have been stronger proof of a direct functional correlation. In addition, there is no evidence to suggest that MDMA has brain region specific effects in terms of its ability to release monoamines, as systemic MDMA administration to rats induces acute release of 5-HT in all forebrain regions, including the striatum, prefrontal cortex, nucleus accumbens, hippocampus and hypothalamus (Green et al 2003;Baumann et al 2008b;Mechan et al 2002;Stanley et al 2007;Benamar et al 2008). It is likely therefore that any 5-HT elevation in the hippocampus mirrors changes produced in other regions.…”

Contributions of serotonin in addiction vulnerability

“…MDMA has dual actions at the 5-HT transporter, blocking 5-HT uptake and inducing non-exocytotic release of 5-HT through reverse transport (Steinkellner et al, 2011). As a consequence, acute MDMA administration elevates extracellular levels of 5-HT in the DRN in vitro (Sprouse et al, 1989; Sprouse et al, 1990; Bradberry et al, 1990; Bradberry et al, 1991; Baumann et al, 2004; Baumann et al, 2005; Renoir et al, 2008) and in the brain in vivo in a number of regions including the nucleus accumbens (White et al, 1994; Kankaanpaa et al, 1998; Baumann et al, 2004; Baumann et al, 2005; O'Shea et al, 2005; Kurling et al, 2008; Baumann et al, 2008b), striatum (Gough et al, 1991; Gudelsky and Nash, 1996; Sabol and Seiden, 1998; Gough et al, 2002; O'Shea et al, 2005; Freezer et al, 2005; Stanley et al, 2007; Baumann et al, 2008b), hippocampus (Gartside et al, 1997; Esteban et al, 2001; Mechan et al, 2002), substantia nigra (Yamamoto et al, 1995; Hewton et al, 2007) and frontal cortex (Gudelsky and Nash, 1996; Gartside et al, 1997; Baumann et al, 2008b). This acute 5-HT stimulatory effect of MDMA then adapts upon subsequent exposures (Rodsiri et al, 2011).…”