This investigation compared anxiety (social and non-social), serotonin and dopamine levels in rats given a low-dose MDMA regimen and rats given a high-dose MDMA regimen. Rats received saline, one dose of 5 mg/kg MDMA, or 4 hourly doses of 5 mg/kg MDMA on 2 consecutive days. 10 weeks post-drug, social anxiety and inclination to social interaction was assessed by observing responses to a novel rat. Non-social anxiety was measured via emergence test (assessing time spent in "hide box" versus in open space, an anxiety-provoking environment for a rat). Twelve weeks post-drug, 18 of 36 rats were killed, and neurochemical analyses were performed on olfactory bulb, prefrontal cortex, striatum, hippocampus and amygdala. Levels of serotonin (5HT), its metabolite 5-hydroxyindoleacetic acid (5HIAA) and dopamine (DA) were performed via HLPC, and serotonin and dopamine transporter levels were measured by measuring general and specific binding of serotonin and dopamine transporter with radioactively labeled drugs. Serotonin 5HT2A and 5HT2C receptor levels were assessed with radioactively labeled DOI (a 5HT2A agonist), and 5HT1A and 5HT1B receptor density was assessed via radiolabeled cyanopindolol, along with the 5HT1B agonist CP 13129 and (separately) the 5HT1A agonist 8-OHDPAT. Both the rats in the "low dose" and "high dose" MDMA conditions spent less time in social interactions than controls, rats given the high dose regimen (but not those given the low-dose regimen) also showed fewer numbers of social interactions when compared to controls. Rats in both the high-dose and low-dose MDMA conditions took longer to emerge from the hide box. Yet only the rats in the high-dose condition showed lower 5HT and 5HIAA in prefrontal cortex, striatum, hippocampus and amygdala than controls. (There were no between-group differences in DA levels). Rats given the high-dose MDMA regimen had lower serotonin transporter (SERT) levels in nearly every brain region checked, while the rats that received low-dose MDMA had lower SERT in medial hypothalamus and higher levels in pyriform and perirhinal/entorhinal cortex. No differences were found between groups on 5HT1A receptor levels. However, low-dose MDMA rats had lower 5HT1B receptor levels in globus pallidus, hippocampus and medial thalamus, and high-dose MDMA rats had lower 5HT1B receptors in globus pallidus, insula and medial thalamus, but higher 5HT1B density in the nucleus accumbens and medial septum. Rats given a low-dose MDMA regimen had significantly lower 5HT2A/2C receptor levels in the pyriform cortex, and a trend for lower 5HT2A/2C receptor levels in "most" brain regions. However, rats given high-dose MDMA regimens had lower 5HT2A/2C receptors in a number of brain regions, including caudate-putamen, insula, cingulate, lateral septum, frontal and entorhinal cortex. 5HT2A/2C receptors in caudate-putamen, lateral septum, medial hypothalamus, medial and lateral thalamus, and entorhinal cortex were lower in high-dose MDMA rats than in low-dose MDMA rats. Study findings demonstrate that both neurotoxic and non-neurotoxic doses of MDMA increase social anxiety, as reported elsewhere (Fone et al. 2002; Mechan et al. 2001), and that reductions or changes in 5HT2A and 5HT1B receptor density, but not 5HT1A receptor density, may be at least partially responsible for this effect. However, only high-dose MDMA produced an increase in non-social anxiety. Other researchers (Reneman et al. 2002) have investigated changes in 5HT2A receptors after MDMA, but they reported an association between reduced brain 5HT and increased 5HT2A receptors 30 days post-drug, whereas neurochemical assessments were made 12 weeks post drug. Overall, study findings suggest that future research into anxiety after MDMA should distinguish between social and non-social anxiety, and that investigators should explore the role played by other serotonin receptors and other neurotransmitters in mediating anxiety. Note that a concurrent publication by the same team examines the effects of the high-dose regimen administered under normal and high ambient temperature. Given that non-neurotoxic doses increased anxiety, these findings suggest that increased anxiety in MDMA treated rodents is a poor indicator of measure of MDMA neurotoxicity.