title: Methamphetamine neurotoxicity: dissociation of striatal dopamine terminal damage from parietal cortical cell body injury.
abstract: Methamphetamine (m-AMPH) administration injures both striatal dopaminergic terminals and certain nonmonoaminergic cortical neurons. Fluoro-Jade histochemistry was used to label cortical cells injured by m-AMPH in order to identify factors that contribute to the cortical cell body damage. Rats given four injections of m-AMPH (4 mg/kg) at 2-h intervals showed hyperthermia (mean = 40.0 +/- 0.10 degrees C) and increased behavioral activation relative to animals given saline (SAL). Three days later, m-AMPH-treated animals showed indices of injury to striatal DA terminals (depletion of tyrosine hydroxylase immunoreactivity) and parietal cortical cell bodies (appearance of Fluoro-Jade stained cells). Pretreatment with a dopamine (DA) D1, D2, or N-methyl-D-aspartate (NMDA) receptor antagonist, or administration of m-AMPH in a 4 degrees C environment, prevented or attenuated m-AMPH-induced hyperthermia, behavioral activation, and injury to striatal DA terminals and parietal cortical cell bodies. Animals pretreated with a DA transport inhibitor prior to m-AMPH showed hyperthermia, behavioral activation, and parietal cortical cell body injury, but they did not show striatal DA terminal injury. Pretreatment with a 5HT transport inhibitor failed to prevent m-AMPH-induced damage to striatal DA terminals or parietal cortical cell bodies. Animals given four injections of SAL in a 37 degrees C environment became hyperthermic, but showed no injury to striatal DA terminals or cortical cell bodies. The ability of the DA transport inhibitor to block m-AMPH-induced striatal DA damage, but not cortical injury, and the inability of hyperthermia alone to cause the cortical cell body injury suggests that m-AMPH-induced behavioral activation and hyperthermia may both be necessary for the subsequent parietal cortical cell body damage.
authors.affiliation: Department of Psychobiology, University of California, Irvine 92697-4550, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Eisch
authors.forename: J F
authors.initials: JF
authors.lastname: Marshall
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000506:poisoning*; D009411:Nerve Endings / Q000187:drug effects; D009474:Neurons / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology*; D010296:Parietal Lobe / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013696:Temperature
chemical_list: D016291:Dizocilpine Maleate; D004298:Dopamine; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D008694:Methamphetamine; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D017367:Selective Serotonin Reuptake Inhibitors