Citation

Johnson EA, O'Callaghan JP, Miller DB. Psychopharmacology 2004; 173(3-4): 278-286.

Affiliation

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

Copyright

(Copyright © 2004, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1007/s00213-003-1740-3

PMID

14735292

Abstract

RATIONALE: 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. OBJECTIVES: 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.

Language: en