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Environment-, drug- and stress-induced alterations in body temperature affect the neurotoxicity of substituted amphetamines in the C57BL/6J mouse.
J Pharmacol Exp Ther 1994; 270(2):752-60JP

Abstract

In the companion paper we demonstrated that d-methamphetamine (d-METH), d-methylenedioxyamphetamine (d-MDA) and d-methylenedioxymethamephetamine (d-MDMA), but not d-fenfluramine (d-FEN), appear to damage dopaminergic projections to the striatum of the mouse. An elevation in core temperature also was associated with exposure to d-METH, d-MDA and d-MDMA, whereas exposure to d-FEN lowered core temperature. Given these findings, we examined the effects of temperature on substituted amphetamine (AMP)-induced neurotoxicity in the C57BL/6J mouse. Levels of striatal dopamine (DA) and glial fibrillary acidic protein (GFAP) were taken as indicators of neurotoxicity. Alterations in ambient temperature, pretreatment with drugs reported to cause hypothermia in the mouse and hypothermia induced by restraint stress were used to affect AMP-induced neurotoxicity. Mice received d-METH (10 mg/kg), d-MDA (20 mg/kg) or d-MDMA (20 mg/kg) every 2 hr for a total of four s.c. injections. All three AMPs increased core temperature and caused large (> 75%) decreases in striatal dopamine and large (> 300%) increases in striatal glial fibrillary acidic protein 72 hr after the last injection. Lowering ambient temperature from 22 degrees C to 15 degrees C blocked (d-MDA and d-MDMA) or severely attenuated (d-METH) these effects. Pretreatment with MK-801 lowered core temperature and blocked AMP-induced neurotoxicity; elevation of ambient temperature during this regimen elevated core temperature and markedly attenuated the neuroprotective effects of MK-801. Pretreatment with MK-801 also lowered core temperature in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice but did not block 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.

Pub Type(s)

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

Language

eng

PubMed ID

8071868

Citation

Miller, D B., and J P. O'Callaghan. "Environment-, Drug- and Stress-induced Alterations in Body Temperature Affect the Neurotoxicity of Substituted Amphetamines in the C57BL/6J Mouse." The Journal of Pharmacology and Experimental Therapeutics, vol. 270, no. 2, 1994, pp. 752-60.
Miller DB, O'Callaghan JP. Environment-, drug- and stress-induced alterations in body temperature affect the neurotoxicity of substituted amphetamines in the C57BL/6J mouse. J Pharmacol Exp Ther. 1994;270(2):752-60.
Miller, D. B., & O'Callaghan, J. P. (1994). Environment-, drug- and stress-induced alterations in body temperature affect the neurotoxicity of substituted amphetamines in the C57BL/6J mouse. The Journal of Pharmacology and Experimental Therapeutics, 270(2), pp. 752-60.
Miller DB, O'Callaghan JP. Environment-, Drug- and Stress-induced Alterations in Body Temperature Affect the Neurotoxicity of Substituted Amphetamines in the C57BL/6J Mouse. J Pharmacol Exp Ther. 1994;270(2):752-60. PubMed PMID: 8071868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Environment-, drug- and stress-induced alterations in body temperature affect the neurotoxicity of substituted amphetamines in the C57BL/6J mouse. AU - Miller,D B, AU - O'Callaghan,J P, PY - 1994/8/1/pubmed PY - 1994/8/1/medline PY - 1994/8/1/entrez SP - 752 EP - 60 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 270 IS - 2 N2 - In the companion paper we demonstrated that d-methamphetamine (d-METH), d-methylenedioxyamphetamine (d-MDA) and d-methylenedioxymethamephetamine (d-MDMA), but not d-fenfluramine (d-FEN), appear to damage dopaminergic projections to the striatum of the mouse. An elevation in core temperature also was associated with exposure to d-METH, d-MDA and d-MDMA, whereas exposure to d-FEN lowered core temperature. Given these findings, we examined the effects of temperature on substituted amphetamine (AMP)-induced neurotoxicity in the C57BL/6J mouse. Levels of striatal dopamine (DA) and glial fibrillary acidic protein (GFAP) were taken as indicators of neurotoxicity. Alterations in ambient temperature, pretreatment with drugs reported to cause hypothermia in the mouse and hypothermia induced by restraint stress were used to affect AMP-induced neurotoxicity. Mice received d-METH (10 mg/kg), d-MDA (20 mg/kg) or d-MDMA (20 mg/kg) every 2 hr for a total of four s.c. injections. All three AMPs increased core temperature and caused large (> 75%) decreases in striatal dopamine and large (> 300%) increases in striatal glial fibrillary acidic protein 72 hr after the last injection. Lowering ambient temperature from 22 degrees C to 15 degrees C blocked (d-MDA and d-MDMA) or severely attenuated (d-METH) these effects. Pretreatment with MK-801 lowered core temperature and blocked AMP-induced neurotoxicity; elevation of ambient temperature during this regimen elevated core temperature and markedly attenuated the neuroprotective effects of MK-801. Pretreatment with MK-801 also lowered core temperature in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice but did not block 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8071868/Environment__drug__and_stress_induced_alterations_in_body_temperature_affect_the_neurotoxicity_of_substituted_amphetamines_in_the_C57BL/6J_mouse_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8071868 DB - PRIME DP - Unbound Medicine ER -