Effect of methamphetamine self-administration on neurotensin systems of the basal ganglia

Paul S. Frankel, Amanda J. Hoonakker, Mario E. Alburges, Jacob W. McDougall, Lisa McFadden, Annette E. Fleckenstein, Glen R. Hanson

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Methamphetamine (METH) dependence causes alarming personal and social damage. Even though many of the problems associated with abuse of METH are related to its profound actions on dopamine (DA) basal ganglia systems, there currently are no approved medications to treat METH addiction. For this reason, we and others have examined the METH-induced responses of neurotensin (NT) systems in the basal ganglia. This neuropeptide is associated with inhibitory feedback pathways to nigrostriatal DA projections, and NT tissue levels are elevated in response to high doses of noncontingent METH because of its increased synthesis in the striatonigral pathway. The present study reports the contingent responses of NT in the basal ganglia to self-administration of METH (SAM). Intravenous infusions of METH linked to appropriate lever-pressing behavior by rats significantly elevated NT content in both dorsal striatum (210%) and substantia nigra (202%). In these same structures, NT levels were also elevated in yoked METH animals (160 and 146%, respectively) but not as much as in the SAM rats. These effects were blocked by a D1, but not D2, antagonist. A NT agonist administered before the day 5 of operant behavior blocked lever-pressing behavior in responding rats, but a NT antagonist had no significant effect on this behavior. These are the first reports that NT systems associated with striatonigral pathway are significantly altered during METH self-administration, and our findings suggest that activation of NT receptors during maintenance of operant responding reduces the associated lever-pressing behavior.

Original languageEnglish (US)
Pages (from-to)809-815
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume336
Issue number3
DOIs
StatePublished - Mar 1 2011

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Neurotensin
Self Administration
Methamphetamine
Basal Ganglia
Dopamine
Neurotensin Receptors
Substantia Nigra
Neuropeptides
Intravenous Infusions
Maintenance

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Frankel, P. S., Hoonakker, A. J., Alburges, M. E., McDougall, J. W., McFadden, L., Fleckenstein, A. E., & Hanson, G. R. (2011). Effect of methamphetamine self-administration on neurotensin systems of the basal ganglia. Journal of Pharmacology and Experimental Therapeutics, 336(3), 809-815. https://doi.org/10.1124/jpet.110.176610

Effect of methamphetamine self-administration on neurotensin systems of the basal ganglia. / Frankel, Paul S.; Hoonakker, Amanda J.; Alburges, Mario E.; McDougall, Jacob W.; McFadden, Lisa; Fleckenstein, Annette E.; Hanson, Glen R.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 336, No. 3, 01.03.2011, p. 809-815.

Research output: Contribution to journalArticle

Frankel, Paul S. ; Hoonakker, Amanda J. ; Alburges, Mario E. ; McDougall, Jacob W. ; McFadden, Lisa ; Fleckenstein, Annette E. ; Hanson, Glen R. / Effect of methamphetamine self-administration on neurotensin systems of the basal ganglia. In: Journal of Pharmacology and Experimental Therapeutics. 2011 ; Vol. 336, No. 3. pp. 809-815.
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