Researchers investigated changes in social and non-social anxiety in young rats, and examined the possible role of changes in 5HT2C receptors in non-social anxiety. All rats received twice-daily injections of 15 mg/kg MDMA on post-natal days (PNDs) 28 to 30. After familiarization with the arena on PND 46, researchers assessed social interaction between treatment and weight-matched pairs of unfamiliar rats on PND 50. On PND 52, the 5HT2C agonist mCPP or saline was administered to MDMA and saline-treated rats, and the researchers measured spontaneous locomotion; on PND 56, mCPP-associated anxiety was measured via elevated plus-maze. MDMA-treated rats demonstrated fewer behaviors indicative of social interaction than saline-treated rats, but they were not less active, and they did not show signs of increased anxiety (such as preferring maze arms with walls to those without them). Both MDMA-treated and saline-treated rats increased behaviors associated with anxiety in the elevated plus maze after receiving mCPP, and corticosterone assessed immediately after plus maze test (with saline or mCPP) was equivalent across groups. Hence it appears that reduced social interaction in MDMA-treated rats is not due to an increase in 5HT2C receptors or 5HT2C receptor sensitivity. Histological examination of hippocampus, striatum and frontal cortex performed 28 days post-MDMA (PND 56) found MDMA-treated animals had lower serotonin (5-HT) and 5HIAA (serotonin metabolite) in hippocampus and frontal cortex, and lower 5HIAA in striatum, indicating MDMA neurotoxicity that the authors describe as moderate. However, MDMA-treated rats did not have lower levels of radiolabelled paroxetine binding, an indirect marker for serotonin transporter sites. Nor did MDMA-treated rats have less elevated plasma corticosterone (rat equivalent of cortisol) after elevated plus maze. This study is also notable for finding hypothermia after MDMA pre-treatment rather than hyperthermia, suggesting a potential difference in response in young ("adolescent") versus adult rats. This report is yet another entry into the literature examining the relationship between MDMA exposure and anxiety in rodents. The authors relate findings to hypotheses proposed by Green (Green and McGregor 2002) concerning levels of pre-existing anxiety and anxiety measured after MDMA. Given only inconclusive findings for MDMA-induced changes in anxiety in rodents, it remains difficult to extrapolate study findings to humans. The authors suggest that not all changes in anxiety may be related to the same pharmacological effects, and that non-neurotoxic doses of MDMA may still affect behavior subsequent to drug administration.
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