Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration

Lisa M. Mcfadden, Amanda J. Hoonakker, Paula L. Vieira-Brock, Kristen A. Stout, Nicole M. Sawada, Jonathan D. Ellis, Scott C. Allen, Elliot T. Walters, Shannon M. Nielsen, James W. Gibb, Mario E. Alburges, Diana G. Wilkins, Glen R. Hanson, Annette E. Fleckenstein

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH duringdevelopment. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity.

Original languageEnglish (US)
Pages (from-to)771-777
Number of pages7
JournalSynapse
Volume65
Issue number8
DOIs
StatePublished - Aug 1 2011

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Methamphetamine
Therapeutics
Induced Hyperthermia
Body Temperature Regulation
Young Adult
Fever
Pharmacokinetics
Maintenance

Keywords

  • Adolescence
  • Methamphetamine
  • Vesicular monoamine transporter-2

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Mcfadden, L. M., Hoonakker, A. J., Vieira-Brock, P. L., Stout, K. A., Sawada, N. M., Ellis, J. D., ... Fleckenstein, A. E. (2011). Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration. Synapse, 65(8), 771-777. https://doi.org/10.1002/syn.20902

Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration. / Mcfadden, Lisa M.; Hoonakker, Amanda J.; Vieira-Brock, Paula L.; Stout, Kristen A.; Sawada, Nicole M.; Ellis, Jonathan D.; Allen, Scott C.; Walters, Elliot T.; Nielsen, Shannon M.; Gibb, James W.; Alburges, Mario E.; Wilkins, Diana G.; Hanson, Glen R.; Fleckenstein, Annette E.

In: Synapse, Vol. 65, No. 8, 01.08.2011, p. 771-777.

Research output: Contribution to journalArticle

Mcfadden, LM, Hoonakker, AJ, Vieira-Brock, PL, Stout, KA, Sawada, NM, Ellis, JD, Allen, SC, Walters, ET, Nielsen, SM, Gibb, JW, Alburges, ME, Wilkins, DG, Hanson, GR & Fleckenstein, AE 2011, 'Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration', Synapse, vol. 65, no. 8, pp. 771-777. https://doi.org/10.1002/syn.20902
Mcfadden, Lisa M. ; Hoonakker, Amanda J. ; Vieira-Brock, Paula L. ; Stout, Kristen A. ; Sawada, Nicole M. ; Ellis, Jonathan D. ; Allen, Scott C. ; Walters, Elliot T. ; Nielsen, Shannon M. ; Gibb, James W. ; Alburges, Mario E. ; Wilkins, Diana G. ; Hanson, Glen R. ; Fleckenstein, Annette E. / Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration. In: Synapse. 2011 ; Vol. 65, No. 8. pp. 771-777.
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