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

Psychopharmacology (Berl). 2014 Aug;231(15):2933-40. doi: 10.1007/s00213-014-3468-7. Epub 2014 Feb 13.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basal Ganglia / drug effects*
  • Basal Ganglia / metabolism*
  • Benzazepines / pharmacology
  • Dopamine Antagonists / pharmacology
  • Dopamine D2 Receptor Antagonists / pharmacology
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Dose-Response Relationship, Drug
  • Male
  • Methamphetamine / administration & dosage*
  • Neurotensin / metabolism*
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Salicylamides / pharmacology
  • Self Administration


  • Benzazepines
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • SCH 23390
  • Salicylamides
  • Neurotensin
  • Methamphetamine
  • eticlopride