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Responses of the rat basal ganglia neurotensin systems to low doses of methamphetamine

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Abstract

Rationale

Administration of high doses of methamphetamine (METH) in a manner mimicking the binging patterns associated with abuse reduces NT release and causes its accumulation and elevated NT levels in extrapyramidal structures by a D1 mechanism. The relevance of these findings to the therapeutic use of METH needs to be studied.

Objectives

The effect of low doses (comparable to that used for therapy) of METH on basal ganglia NT systems was examined and compared to high-dose and self-administration effects previously reported.

Methods

Rats were injected four times (2-h intervals) with either saline or low doses of METH (0.25, 0.50, or 1.00 mg/kg/subcutaneously (s.c.)). For the DA antagonist studies, animals were pretreated with a D1 (SCH23390) or D2 (eticlopride) antagonist 15 min prior to METH or saline treatments. Rats were sacrificed 5–48 h after the last injection.

Results

METH at doses of 0.25 and 0.50, but not 1.00 mg/kg, rapidly and briefly decreased NTLI concentration in all basal ganglia structures studied. In the posterior dorsal striatum, the reduction in NT level after low-dose METH appeared to be caused principally by D2 stimulation, but both D2 and D1 stimulation were required for the NT responses in the other basal ganglia regions.

Conclusions

A novel finding from the present study was that opposite to abuse-mimicking high doses of METH, the therapeutically relevant low-dose METH treatment reduced NT tissue levels likely reflecting an increase in NT release and a short-term depletion of the levels of this neuropeptide in basal ganglia structures. The possible significance is discussed.

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Acknowledgments

This work was supported by U.S. Public Health Service Grants DA031883, DA, DA013367, and DA000378. The experiments described within this publication are all in compliance with the laws of the USA.

Conflict of interest

The authors declare that they have no biomedical financial interests or other conflicts of interest.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, RM 201, Salt Lake City, UT, 84112, USA

    Mario E. Alburges, Amanda J. Hoonakker, Nathaniel M. Cordova, Christina M. Robson, Lisa M. McFadden, Amber L. Martin & Glen R. Hanson

  2. School of Dentistry, University of Utah, Salt Lake City, UT, USA

    Glen R. Hanson

Authors
  1. Mario E. Alburges
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  2. Amanda J. Hoonakker
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  3. Nathaniel M. Cordova
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  4. Christina M. Robson
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  5. Lisa M. McFadden
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  6. Amber L. Martin
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  7. Glen R. Hanson
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Correspondence to Mario E. Alburges.

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Alburges, M.E., Hoonakker, A.J., Cordova, N.M. et al. Responses of the rat basal ganglia neurotensin systems to low doses of methamphetamine. Psychopharmacology 231, 2933–2940 (2014). https://doi.org/10.1007/s00213-014-3468-7

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  • DOI: https://doi.org/10.1007/s00213-014-3468-7

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