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Neuroadaptive Changes in 5-HT1A Autoreceptor Sensitivity Following High-Dose MDMA Treatment

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Version 3 2023-03-14, 23:27
Version 2 2023-03-13, 23:55
Version 1 2021-11-10, 22:50
posted on 2023-03-14, 23:27 authored by Fisher, Simon David

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.


Copyright Date


Date of Award



Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains Copyright

Degree Discipline

Cognitive and Behavioural Neuroscience

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level


Degree Name

Master of Science

Victoria University of Wellington Item Type

Awarded Research Masters Thesis



Victoria University of Wellington School

School of Psychology


Schenk, Susan