α-Phenyl-N-tert-butyl nitrone attenuates methamphetamine-induced depletion of striatal dopamine without altering hyperthermia

G. D. Cappon, H. W. Broening, Cunfeng Pu, L. Morford, C. V. Vorhees

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Methamphetamine (MA) administration to adult rats (4 x 10 mg/kg s.c.) induces neurotoxicity predominately characterized by a persistent reduction of neostriatal dopamine (DA) content. Hyperthermia following MA administration potentiates the resulting DA depletion. DA-derived free radicals are postulated to be a mechanism through which MA-induced neurotoxicity is produced. The spin trapping agent PBN reacts with free radicals to form nitroxyl adducts, thereby preventing damaging free radical reactions with cellular substrates. MA with saline pretreatment (Sal-MA) reduced neostriatal DA by 55% (P < 0.01 vs. Sal-Sal). MA with PBN pretreatment (PBN-MA) at 36 or 60 mg/kg reduced neostriatal DA by 36 and 22%, respectively (P < 0.05 and P < 0.01 vs. Sal-MA) indicating partial protection. PBN pretreatment did not alter MA-induced hyperthermia. Thus, PBN does not attenuate MA-induced neurotoxicity by reducing MA-induced hyperthermia. These results support a role for free radicals in the generation of MA-induced dopaminergic neurotoxicity.

Original languageEnglish (US)
Pages (from-to)173-181
Number of pages9
JournalSynapse
Volume24
Issue number2
DOIs
StatePublished - Oct 1 1996

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Corpus Striatum
Methamphetamine
Dopamine
Fever
Free Radicals
Induced Hyperthermia
nitrones
Spin Trapping

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Cappon, G. D. ; Broening, H. W. ; Pu, Cunfeng ; Morford, L. ; Vorhees, C. V. / α-Phenyl-N-tert-butyl nitrone attenuates methamphetamine-induced depletion of striatal dopamine without altering hyperthermia. In: Synapse. 1996 ; Vol. 24, No. 2. pp. 173-181.
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α-Phenyl-N-tert-butyl nitrone attenuates methamphetamine-induced depletion of striatal dopamine without altering hyperthermia. / Cappon, G. D.; Broening, H. W.; Pu, Cunfeng; Morford, L.; Vorhees, C. V.

In: Synapse, Vol. 24, No. 2, 01.10.1996, p. 173-181.

Research output: Contribution to journalArticle

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AU - Morford, L.

AU - Vorhees, C. V.

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