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Brain concentrations of d-MDMA are increased after stress.
Psychopharmacology (Berl) 2004; 173(3-4):278-86P

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.

Authors+Show Affiliations

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.govNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14735292

Citation

Johnson, Elizabeth Anne, et al. "Brain Concentrations of d-MDMA Are Increased After Stress." Psychopharmacology, vol. 173, no. 3-4, 2004, pp. 278-86.
Johnson EA, O'Callaghan JP, Miller DB. Brain concentrations of d-MDMA are increased after stress. Psychopharmacology (Berl). 2004;173(3-4):278-86.
Johnson, E. A., O'Callaghan, J. P., & Miller, D. B. (2004). Brain concentrations of d-MDMA are increased after stress. Psychopharmacology, 173(3-4), pp. 278-86.
Johnson EA, O'Callaghan JP, Miller DB. Brain Concentrations of d-MDMA Are Increased After Stress. Psychopharmacology (Berl). 2004;173(3-4):278-86. PubMed PMID: 14735292.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain concentrations of d-MDMA are increased after stress. AU - Johnson,Elizabeth Anne, AU - O'Callaghan,James P, AU - Miller,Diane B, Y1 - 2004/01/20/ PY - 2003/09/23/received PY - 2003/11/26/accepted PY - 2004/1/22/pubmed PY - 2004/12/16/medline PY - 2004/1/22/entrez SP - 278 EP - 86 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 173 IS - 3-4 N2 - 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/14735292/Brain_concentrations_of_d_MDMA_are_increased_after_stress_ L2 - https://dx.doi.org/10.1007/s00213-003-1740-3 DB - PRIME DP - Unbound Medicine ER -