Journal
SYNAPSE
Volume 61, Issue 7, Pages 478-487Publisher
WILEY-LISS
DOI: 10.1002/syn.20377
Keywords
MDMA; DASB; serotonin receptors; serotonin transporters; pig; toxicity
Categories
Ask authors/readers for more resources
The psychostimulant 3,4-methylendioxymethamphetamine (MDMA, ecstasy) evokes degeneration of telencephalic serotonin innervations in rodents, nonhuman primates, and human recreational drug users. However, there has been no alternative to nonhuman primates for studies of the cognitive and neurochemical consequences of serotonin depletion in a large-bodied animal. Therefore, we used positron emission tomography (PET) with [C-11]DASB to map the distribution of plasma membrane serotonin transporters in brain of Gottingen minipigs, first in a baseline condition, and again at 2 weeks after treatment with MDMA (i.m.), administered at a range of doses. In parallel PET studies, [C-11]WAY-100635 was used to map the distribution of serotonin 5HT(1A) receptors. The acute MDMA treatment in awake pigs evoked 1 degrees C of hyperthermia. MDMA at total doses greater than 20 mg/kg administered over 2-4 days reduced the binding potential (pB) of [C-11]DASB for serotonin transporters in porcine brain. A mean total dose of 42 mg/kg MDMA in four animals evoked a mean 32% decrease in [11(C)]DASB pB in mesencephalon and diencephalon, and a mean 53% decrease in telencephalic structures. However, this depletion of serotonin innervations was not associated with consistent alterations in the binding of [C-11]WAY-100635 to serotonin 5HT(1A) receptors. Stereological cell counting of serotonin-positive neurons, which numbered 95,000 in the dorsal raphe nucleus of normal animals, was unaffected in MDMA-treated group.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available