Brain concentrations of d-MDMA are increased after stress.
BACKGROUND
In the mouse but not the rat, d-3,4-methylenedioxymethamphetamine (d-MDMA) is a dopaminergic neurotoxicant. Various stressors and hypothermia protect against d-MDMA-induced neurotoxicity through unknown mechanisms, one of which could be a reduction in the distribution of d-MDMA to the brain.


OBJECTIVE
We determined striatal levels of d-MDMA in relation to body temperature in mice exposed to a neurotoxic regimen of d-MDMA in the presence or absence of various stressors.


METHODS
Female C57BL6/J mice received a neurotoxic regimen of d-MDMA (15.0 mg/kg s.c. as the base every 2 hx4) alone or in combination with manipulations with a known neuroprotective status. d-MDMA levels were determined by HPLC with fluorometric detection while rectal temperature provided core temperature status. Levels of dopamine, tyrosine hydroxylase and GFAP were used to assess neurotoxicity.


RESULTS
Restraint, ethanol co-treatment and cold stress were neuroprotective, caused hypothermia and increased striatal d-MDMA levels by 4- to 7-fold. Corticosterone treatment, as a stress mimic, did not alter striatal d-MDMA or temperature and was not protective. The protective glutamate receptor antagonist, MK-801, doubled striatal d-MDMA levels and caused hypothermia.


CONCLUSIONS
Although stress and other protective manipulations can alter the striatal concentration of d-MDMA their hypothermia-inducing properties appear a more likely determinant of their neuroprotection against the striatal dopaminergic neurotoxicity of d-MDMA.
Johnson
Elizabeth Anne
EA
Chronic Stress Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health/Centers for Disease Control, 1095 Willowdale Road, Morgantown, VA 26505, USA. EDJ2@cdc.gov
O'Callaghan
James P
JP
Miller
Diane B
DB
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003080:Cold Temperature / Q000009:adverse effects; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control; D012149:Restraint, Physical; D013237:Stereoisomerism; D013315:Stress, Psychological / Q000209:etiology / Q000378:metabolism*
D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine