Developmental neurotoxicity to methamphetamines.
1. To investigate the long-term changes caused by amphetamines in the developing brain, we used both an in vivo and in vitro model of chronic fetal exposure to methamphetamine and related drugs. 2. Offspring of rats, treated with either saline, 2 mg/kg twice a day (b.i.d.) or 10 mg/kg b.i.d. methamphetamine throughout gestation, were examined at 30 days of age for changes in the monoamine system of their brains. 3. At the lower dose methamphetamine was neurotoxic to specific neuronal populations, mostly serotonergic. At the higher dose, methamphetamine retained its neurotoxic properties, but also stimulated the growth of axonal terminals in specific regions as evidenced by an increase in monoamine uptake sites. The neurochemical changes at the higher dose were correlated with deficits in adult behavioural measures. 4. Corresponding in vitro drug treatments of rat neuroblastomas cells also produced a dose-related effect on cellular growth and differentiation patterns. Neurotoxic as well as stimulatory effects of methamphetamine and some related compounds were seen in culture. 5. Our in vivo and in vitro observations demonstrate neurotoxic effects of amphetamines and the remodelling of synaptic morphology in response.
Weissman
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Seton Hall University, School of Graduate Medical Education, South Orange, New Jersey, USA.
Caldecott-Hazard
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S
D000588:Amines / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D008694:Methamphetamine / Q000031:analogs & derivatives / Q000633:toxicity*; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D014407:Tumor Cells, Cultured
D000588:Amines; D000697:Central Nervous System Stimulants; D008694:Methamphetamine