Abstract:
Rationale: There is evidence that the serotonin (5-HT) deficits and related
cognitive and mood impairments caused by +/-3,4-
methylenedioxymethamphetamine (MDMA) may be mediated by
neuroadaptations of the 5-HT1A autoreceptor.
Objectives: The increase in sensitivity of the 5-HT1A autoreceptor caused by highdose,
repeated MDMA treatment was assessed neurochemically, by measuring 5-
HTP accumulation, and physiologically, via changes in body temperature.
Methods: Experiment 1 confirmed the effects of 8-hydroxy-2-(di-npropylamino)
tetralin (8-OH-DPAT) (0, 0.025, 0.05, 0.1 mg/kg s.c.) on 5-
hydroxytryptophan (5-HTP) accumulation following 3-hydroxybenzylhydrazine
dihydrochloride (NSD-1015) administration as a valid measure of 5-HT synthesis
and hence 5-HT1A autoreceptor sensitivity in rats. Experiment 2 performed these
procedures in additional animals, with half receiving MDMA (4x 10 mg/kg i.p. at
2 hour intervals) two weeks before testing. Body temperature changes due to the
8-OH-DPAT hypothermic response were tested using a rectal probe. Experiment
2b repeated the procedures in additional groups with lower doses of 8-OH-DPAT
(0.0125 and 0.00625 mg/kg s.c.).
Results: No significant changes in 5-HTP accumulation levels or changes in the
hypothermic response to 8-OH-DPAT were found between MDMA pretreated
rats and controls in Experiments 2 and 2b. Moreover, there was no substantial
evidence of expected 5-HT deficits due to high-dose MDMA treatment.
Conclusion: The results do not indicate an increase in sensitivity of the 5-HT1A
autoreceptor, and hence the original hypothesis is not supported. However, there
were a number of methodological issues, as indicated by the lack of MDMAinduced
5-HT deficits, which prevent a firm conclusion from being drawn. Future
research is outlined to overcome these issues.
