Chronic nicotine exposure attenuates methamphetamine-induced dopaminergic deficits

Paula L. Vieira-Brock, Lisa M. McFadden, Shannon M. Nielsen, Jonathan D. Ellis, Elliot T. Walters, Kristen A. Stout, J. Michael McIntosh, Diana G. Wilkins, Glen R. Hanson, Annette E. Fleckenstein

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Repeated methamphetamine (METH) administrations cause persistent dopaminergic deficits resembling aspects of Parkinson's disease. Many METH abusers smoke cigarettes and thus selfadminister nicotine; yet few studies have investigated the effects of nicotine on METH-induced dopaminergic deficits. This interaction is of interest because preclinical studies demonstrate that nicotine can be neuroprotective, perhaps owing to effects involving α4β2 and α6β2 nicotinic acetylcholine receptors (nAChRs). This study revealed that oral nicotine exposure beginning in adolescence [postnatal day (PND) 40] through adulthood [PND 96] attenuated METH-induced striatal dopaminergic deficits when METH was administered at PND 89. This protection did not appear to be due to nicotine-induced alterations in METH pharmacokinetics. Short-term (i.e., 21-day) high-dose nicotine exposure also protected when administered from PND 40 to PND 61 (with METH at PND 54), but this protective effect did not persist. Short-term (i.e., 21-day) high-dose nicotine exposure did not protect when administered postadolescence (i.e., beginning at PND 61, with METH at PND 75). However, protection was engendered if the duration of nicotine exposure was extended to 39 days (with METH at PND 93). Autoradiographic analysis revealed that nicotine increased striatal α4β2 expression, as assessed using [125I]epibatidine. Both METH and nicotine decreased striatal α6β2 expression, as assessed using [125I]aconotoxin MII. These findings indicate that nicotine protects against METH-induced striatal dopaminergic deficits, perhaps by affecting α4β2 and/or α6β2 expression, and that both age of onset and duration of nicotine exposure affect this protection.

Original languageEnglish (US)
Pages (from-to)463-472
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
StatePublished - Dec 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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