Ontogeny of methamphetamine-induced neurotoxicity and associated hyperthermic response

被引:73
作者
Cappon, GD
Morford, LL
Vorhees, CV
机构
[1] CHILDRENS HOSP RES FDN,DIV DEV BIOL,PROGRAM NEUROSCI,CINCINNATI,OH 45229
[2] UNIV CINCINNATI,DEPT PEDIAT,CINCINNATI,OH 45229
来源
DEVELOPMENTAL BRAIN RESEARCH | 1997年 / 103卷 / 02期
关键词
methamphetamine; neurotoxicity; GFAP; dopamine; serotonin; caudate-putamen; development;
D O I
10.1016/S0165-3806(97)81791-9
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Methamphetamine (MA) administration to adult rats results in neurotoxicity characterized by depletion of caudate-putamen (CP) dopamine (DA) and serotonin (5-HT) and an accompanying increase in glial fibrillary acidic protein (GFAP) content. The severity of MA-induced neurotoxicity correlates with the accompanying thermoregulatory response, i.e., a hyperthermic response facilitates neurotoxicity while a hypothermic response is neuroprotective. In the following study, the thermoregulatory and neurotoxic effects of MA administration (4 X 10 mg/kg) were investigated in developing rats at postnatal days (PND) 20, 40 and 60. Rats at PND 20 and PND 40 were administered MA at ambient temperatures of 22 degrees C and 30 degrees C; and PND 60 rats were administered MA at 22 degrees C only. Temperatures were measured and thermal responses were compared by calculating the total thermal response (TTR) induced by MA treatment. MA administration to PND 60 rats at 22 degrees C induced a hyperthermic response, resulted in a 47% reduction of neostriatal DA and a 49% increase of GFAP content. Administration of MA to PND 40 rats at 22 degrees C failed to induce a hyperthermic response and did not result in reduced DA or increased GFAP. However, administration of MA to PND 40 rats at 30 degrees C induced hyperthermia, reduced neostriatal DA by 54% and increased GFAP by 70%. MA administration to PND 20 rats at either 22 degrees C or 30 degrees C did not result in DA depletion or increased GFAP, even though MA administration to PND 20 rats at 30 degrees C induced hyperthermia. These results demonstrate that the induction of hyperthermia is necessary to exhibit MA-induced neurotoxicity at PND 40; however, PND 20 rats are resistant to the DA depleting effects of MA despite the induction of hyperthermia. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:155 / 162
页数:8
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